subject:(Immune checkpoint)

1. Wu, Ching-Lien. Study of the immune checkpoint HLA-G/ILT2 : soluble receptors, inhibition of iNKT cells : Etude du checkpoint inhibiteur HLA-G/ILT2 : récepteurs solubles, inhibition des cellules iNKT.

Degree: Docteur es, Médecine. Biothérapies, 2018, Sorbonne Paris Cité

URL: http://www.theses.fr/2018USPCC188

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HLA-G est une molécule checkpoint immunologique tolérogène connue pour son rôle dans la tolerance materno-foetale, puis comme mécanisme d’échappement immunitaire des tumeurs. HLA-G exerce ses… (more)

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HLA-G est une molécule checkpoint immunologique tolérogène connue pour son rôle dans la tolerance materno-foetale, puis comme mécanisme d’échappement immunitaire des tumeurs. HLA-G exerce ses fonctions via avec deux récepteurs inhibiteurs principaux, ILT2 et ILT4, différentiellement exprimés par les effecteurs immunitaires. L’expression de HLA-G par les tumeurs solides est associée à de plus hauts grades et à un pronostic plus sévère. Pour ces raisons, HLA-G et ses récepteurs pourraient constituer de bonnes cibles immuno-thérapeutiques en oncologie.Ce travail de doctorat a porté sur 1) l’existence et la pertinence clinique des formes solubles de ILT2 et ILT4, ainsi que sur 2) la fonction de la molécule HLA-G sur les cellules iNKT.1) Existence et pertinence clinique des formes solubles de ILT2 et ILT4 : nous avons tout d’abord développé un test Luminex de dosage des formes solubles de ILT2 et ILT4. Ce test est spécifique des molecules sILT2 et sILT4 libres (i.e. non complexées à HLA-G) et nous a permis d’établir que des formes solubles de ILT2 existaient in vivo et circulaient dans le sang périphérique. Cependant, nos cohortes ne nous ont pas permis de détecter des formes solubles d’ILT4 circulantes. Nous avons mesuré les niveaux de sILT2 et sILT4 dans le sang périphérique de (i) patients atteints de cancers de type B-CLL, lymphome B et cancer de vessie non-infiltrant le muscle, (ii) patients atteints de dégénérescence maculaire liée à l’âge, et (iii) patients atteints de troubles bipolaires. Malgré des niveaux de sILT2 plus élevés chez certains patients atteints de cancer, nos études n’ont pas permis d’atteindre de pertinence statistique.2) Fonctions de la molécule HLA-G sur les cellules iNKT : les cellules iNKT ont été décrites comme inductrices de réponses anti-tumorales dans des modèles expérimentaux murins et font l’objet d’études à visée thérapeutique comme outils immuno-thérapeutiques soit par elles-mêmes, soit comme adjuvants. Les cellules iNKT sont une sous-population minoritaire de lymphocytes T qui reconnaissent des lipides présentés dans le context de CD1d. HLA-G étant communément exprimée par les tumeurs humaines, il est donc important de caractériser sa function sur les cellules iNKT. Nos travaux démontrent que les cellules iNKT n’expriment que très peu ILT2, mais que cette expression est induite par l’activation. Nous avons aussi démontré que HLA-G inhibe la production cytokinique des cellules iNKT, soit directement via ILT2, soit indirectement par l’intermédiaire de cellules myeloides tolérogènes. Ces résultats démontrent l’intérêt d’étudier HLA-G et ses récepteurs ILT2 et ILT4 concommitamment et suggèrent que le blocage du checkpoint immunologique HLA-G/ILT2 constitue une stratégie adjuvante valide afin d’améliorer l’efficacité des immunothérapies visant des tumeurs exprimant HLA-G.

HLA-G is a tolerogenic immune checkpoint molecule, first known for its role in maternal-fetal tolerance and now well described as an immune escape mechanism for tumors. HLA-G exerts its functions through interaction…

Advisors/Committee Members: LeMaoult, Joël (thesis director).

Subjects/Keywords: ILT2; ILT4; Checkpoint inhibiteur; ILT2; ILT4; Immune checkpoint

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APA (6^th Edition):

Wu, C. (2018). Study of the immune checkpoint HLA-G/ILT2 : soluble receptors, inhibition of iNKT cells : Etude du checkpoint inhibiteur HLA-G/ILT2 : récepteurs solubles, inhibition des cellules iNKT. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCC188

Chicago Manual of Style (16^th Edition):

Wu, Ching-Lien. “Study of the immune checkpoint HLA-G/ILT2 : soluble receptors, inhibition of iNKT cells : Etude du checkpoint inhibiteur HLA-G/ILT2 : récepteurs solubles, inhibition des cellules iNKT.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 16, 2021. http://www.theses.fr/2018USPCC188.

MLA Handbook (7^th Edition):

Wu, Ching-Lien. “Study of the immune checkpoint HLA-G/ILT2 : soluble receptors, inhibition of iNKT cells : Etude du checkpoint inhibiteur HLA-G/ILT2 : récepteurs solubles, inhibition des cellules iNKT.” 2018. Web. 16 Jan 2021.

Vancouver:

Wu C. Study of the immune checkpoint HLA-G/ILT2 : soluble receptors, inhibition of iNKT cells : Etude du checkpoint inhibiteur HLA-G/ILT2 : récepteurs solubles, inhibition des cellules iNKT. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2018USPCC188.

Council of Science Editors:

Wu C. Study of the immune checkpoint HLA-G/ILT2 : soluble receptors, inhibition of iNKT cells : Etude du checkpoint inhibiteur HLA-G/ILT2 : récepteurs solubles, inhibition des cellules iNKT. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCC188

2. Santry, Lisa. Production of Preclinical Grade Recombinant Newcastle disease viruses to Enhance Tumor Specific Immune Responses in Syngeneic Mouse Models of Cancer.

Degree: PhD, Department of Pathobiology, 2018, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12313

► Oncolytic virus (OV) therapy is an experimental form of biological therapy has shown increasing potential over the last decade, culminating with the first FDA approval… (more)

▼ Oncolytic virus (OV) therapy is an experimental form of biological therapy has shown increasing potential over the last decade, culminating with the first FDA approval of an OV therapy, the Herpes simplex virus Talimogene laherparepvec (T-VEC), in 2015. Newcastle disease virus (NDV), a promising OV with a strong safety record, preferentially replicates in and kills established cancer cells, while leaving normal cells untouched. While NDV can activate and prime the immune system to recognize malignant cells, cytotoxic T cells can ultimately be inhibited in the highly immune suppressive milieu of the tumor microenvironment. To counter these immune suppressive roadblocks, we hypothesize that arming NDV with immune checkpoint blockades, including a humanized CTLA-4 antibody and soluble PD-1, will prevent T cell shutdown and localize expression of these biologics to the tumor. Described herein are methods and experiments to test this hypothesis. We optimized a protocol for efficient rescue of rNDV in embryonated chicken eggs and found that both tangential flow filtration and interference chromatography are feasible methods for the purification of high-titer, ultra-clean suitable for systemic delivery in murine cancer models. Additionally, we characterized a panel of murine cancer cell lines to determine the most appropriate model to test vectorization of NDV. We discovered that murine melanoma (B16-F10) cells are most susceptible to NDV oncolysis, but die too quickly to support much transgene expression, whereas a cell line like the murine colon carcinoma CT26LacZ cells, which are not able to produce or respond to IFN, are less susceptible to NDV-mediated oncolysis but can support reasonable levels of virus replication and transgene expression. Finally, we evaluated rNDVs expressing immune checkpoint blockades in vivo in CT26LacZ and B16-F10 cancer models and observed a promising increase in the ratios of activated CD8+ T cells to suppressive T regulatory and myeloid derived suppressor cells, which have been shown to be important indicators of outcome, in mice treated with rNDV expressing checkpoint inhibitors compared to controls. These results demonstrate that arming NDV with immune checkpoint blockades warrants further investigation as a potential therapeutic agent for cancer treatment in humans. Advisors/Committee Members: Wootton, Sarah (advisor).

Subjects/Keywords: Newcastle disease virus; NDV; murine melanoma; murine colon carcinoma; oncolytic virus; immune checkpoint inhibitor; immune checkpoint blockade; cancer immunotherapy; virus purification

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APA (6^th Edition):

Santry, L. (2018). Production of Preclinical Grade Recombinant Newcastle disease viruses to Enhance Tumor Specific Immune Responses in Syngeneic Mouse Models of Cancer. (Doctoral Dissertation). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12313

Chicago Manual of Style (16^th Edition):

Santry, Lisa. “Production of Preclinical Grade Recombinant Newcastle disease viruses to Enhance Tumor Specific Immune Responses in Syngeneic Mouse Models of Cancer.” 2018. Doctoral Dissertation, University of Guelph. Accessed January 16, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12313.

MLA Handbook (7^th Edition):

Santry, Lisa. “Production of Preclinical Grade Recombinant Newcastle disease viruses to Enhance Tumor Specific Immune Responses in Syngeneic Mouse Models of Cancer.” 2018. Web. 16 Jan 2021.

Vancouver:

Santry L. Production of Preclinical Grade Recombinant Newcastle disease viruses to Enhance Tumor Specific Immune Responses in Syngeneic Mouse Models of Cancer. [Internet] [Doctoral dissertation]. University of Guelph; 2018. [cited 2021 Jan 16]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12313.

Council of Science Editors:

Santry L. Production of Preclinical Grade Recombinant Newcastle disease viruses to Enhance Tumor Specific Immune Responses in Syngeneic Mouse Models of Cancer. [Doctoral Dissertation]. University of Guelph; 2018. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/12313

University of Arizona

3. Almutairi, Abdulaali R. Immune-Related Adverse Events (irAEs) of Immune Checkpoint Inhibitors (ICIs) in Advanced Melanoma Patients .

Degree: 2020, University of Arizona

URL: http://hdl.handle.net/10150/641423

► Abstract (1): Background: The use of ipilimumab, nivolumab, and pembrolizumab as monotherapies or in combination has transformed the management of advanced melanoma even though these… (more)

▼ Abstract (1): Background: The use of ipilimumab, nivolumab, and pembrolizumab as monotherapies or in combination has transformed the management of advanced melanoma even though these drugs are associated with a new profile of immune-related adverse events (irAEs). The incidence of irAEs from clinical trials of these agents is an important factor for clinicians when treating patients with advanced melanoma. In the current study, we aimed to profile the incidence of potential irAEs of these agents when used as monotherapy and as combination therapy. Methods: We searched the Medline, Embase, and Cochrane databases; clinicaltrials.gov; and websites of regulatory agencies in the USA, Europe, Australia, and Japan for phase 1-3 trials of ipilimumab, nivolumab, and pembrolizumab for advanced melanoma. Random effect meta-analysis was utilized to profile the incidence of potential irAEs. Results: A total of 58 reports of 35 trials including 6331 patients with advanced melanoma and reporting irAE data were included in the meta-analyses. We found higher incidences of potential irAEs in combination therapies versus monotherapies for most of the types of irAEs. Among the monotherapies, ipilimumab users had the most frequent incidence of potential irAEs related to the gastrointestinal system (diarrhea, 29%; and colitis, 8%) and skin (rash, 31%; pruritus, 27%; and dermatitis, 10%), with hypophysitis in 4% of the patients. The most frequent potential irAEs among nivolumab users were maculopapular rash (13%), erythema (4%), hepatitis (3%), and infusion-related reactions (3%), while they were arthralgia (12%), hypothyroidism (8%), and hyperglycemia (6%) among pembrolizumab users. Conclusion: Especially the combination therapies tend to elevate the incidence of potential irAEs. Clinicians should be vigilant about irAEs following combination therapy as well as gastrointestinal and skin irAEs following ipilimumab therapy, in addition to being aware of potential irAEs leading to hyperglycemia, thyroid, hepatic, and musculoskeletal disorders following nivolumab and pembrolizumab therapy. Abstract (2): Importance Anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) antibody (ipilimumab) and anti-programmed cell death 1(anti-PD1) antibodies (nivolumab and pembrolizumab), have been shown to have a beneficial effect in treating melanoma but their risk of immune-related hypothyroidism (ir-hypothyroidism) in elderly patients from a real-world setting is limited. Objective To estimate the risk of ir-hypothyroidism in elderly with advanced melanoma treated with anti-CTLA4 or anti-PD1 in real-world setting. Design, Setting, and Participants SEER-Medicare data was used to identify elderly patients (≥65 years) diagnosed with advanced melanoma between 2011 and 2015 who were de novo users of anti-CTLA4 or anti-PD1. We estimated the risk of ir-hypothyroidism between users of anti-PD1 and anti-CTLA4. We used a propensity weighting approach by using the inverse probability of treatment weighting (IPTW) method to adjust for potential confounders. We utilized… Advisors/Committee Members: Abraham, Ivo (advisor), Erstad, Brian (committeemember), Slack, Marion (committeemember), Mcbride, Ali (committeemember).

Subjects/Keywords: colitis; hypothyroidism; immune checkpoint inhibitors; Immune-Related Adverse Events; melanoma; real-world

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APA (6^th Edition):

Almutairi, A. R. (2020). Immune-Related Adverse Events (irAEs) of Immune Checkpoint Inhibitors (ICIs) in Advanced Melanoma Patients . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/641423

Chicago Manual of Style (16^th Edition):

Almutairi, Abdulaali R. “Immune-Related Adverse Events (irAEs) of Immune Checkpoint Inhibitors (ICIs) in Advanced Melanoma Patients .” 2020. Doctoral Dissertation, University of Arizona. Accessed January 16, 2021. http://hdl.handle.net/10150/641423.

MLA Handbook (7^th Edition):

Almutairi, Abdulaali R. “Immune-Related Adverse Events (irAEs) of Immune Checkpoint Inhibitors (ICIs) in Advanced Melanoma Patients .” 2020. Web. 16 Jan 2021.

Vancouver:

Almutairi AR. Immune-Related Adverse Events (irAEs) of Immune Checkpoint Inhibitors (ICIs) in Advanced Melanoma Patients . [Internet] [Doctoral dissertation]. University of Arizona; 2020. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10150/641423.

Council of Science Editors:

Almutairi AR. Immune-Related Adverse Events (irAEs) of Immune Checkpoint Inhibitors (ICIs) in Advanced Melanoma Patients . [Doctoral Dissertation]. University of Arizona; 2020. Available from: http://hdl.handle.net/10150/641423

4. Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita, Hideo. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo : PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果.

Degree: 博士（医学）, 2013, Nara Medical University / 奈良県立医科大学

URL: http://hdl.handle.net/10564/2588

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Recent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has… (more)

Subjects/Keywords: PD-1; VEGFR2; Immune checkpoint; Antiangiogenesis; Antitumour immunity

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APA (6^th Edition):

Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita, H. (2013). Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo : PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果. (Thesis). Nara Medical University / 奈良県立医科大学. Retrieved from http://hdl.handle.net/10564/2588

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita, Hideo. “Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo : PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果.” 2013. Thesis, Nara Medical University / 奈良県立医科大学. Accessed January 16, 2021. http://hdl.handle.net/10564/2588.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita, Hideo. “Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo : PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果.” 2013. Web. 16 Jan 2021.

Vancouver:

Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita H. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo : PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果. [Internet] [Thesis]. Nara Medical University / 奈良県立医科大学; 2013. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10564/2588.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yasuda, Satoshi; Sho, Masayuki; Yamato, Ichiro; Yoshiji, Hitoshi; Wakatsuki, Kohei; Nishiwada, Satoshi; Yagita H. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo : PD-1とVEGFR2の同時阻害による相乗的抗腫瘍効果. [Thesis]. Nara Medical University / 奈良県立医科大学; 2013. Available from: http://hdl.handle.net/10564/2588

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

UCLA

5. Palaskas, Nicolaos Jay. A platform for investigating immune checkpoint-mediated changes in metabolism.

Degree: Molec, Cell, & Integ Physiology, 2017, UCLA

URL: http://www.escholarship.org/uc/item/25011272

► There is a growing interest in metabolomic profiling of immune cells, as there is accumulating evidence that metabolism influences immune cell function and fate decisions.… (more)

Subjects/Keywords: Immunology; immune checkpoint; immunometabolism; mass spectrometry; metabolomics; PD-1; platform

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APA (6^th Edition):

Palaskas, N. J. (2017). A platform for investigating immune checkpoint-mediated changes in metabolism. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/25011272

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Palaskas, Nicolaos Jay. “A platform for investigating immune checkpoint-mediated changes in metabolism.” 2017. Thesis, UCLA. Accessed January 16, 2021. http://www.escholarship.org/uc/item/25011272.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Palaskas, Nicolaos Jay. “A platform for investigating immune checkpoint-mediated changes in metabolism.” 2017. Web. 16 Jan 2021.

Vancouver:

Palaskas NJ. A platform for investigating immune checkpoint-mediated changes in metabolism. [Internet] [Thesis]. UCLA; 2017. [cited 2021 Jan 16]. Available from: http://www.escholarship.org/uc/item/25011272.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Palaskas NJ. A platform for investigating immune checkpoint-mediated changes in metabolism. [Thesis]. UCLA; 2017. Available from: http://www.escholarship.org/uc/item/25011272

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

6. Garcia-Neuer, Marlene. Systematic diagnostic evaluation for immune-related colitis: a single institutional review of advanced melanoma patients treated with ipilimumab.

Degree: MS, Clinical Investigation, 2016, Boston University

URL: http://hdl.handle.net/2144/17019

► Colitis can be a life-threatening immune-related adverse event (irAE) for patients with metastatic melanoma treated with immune checkpoint blockade, a new anti-cancer immunotherapy. With the… (more)

▼ Colitis can be a life-threatening immune-related adverse event (irAE) for patients with metastatic melanoma treated with immune checkpoint blockade, a new anti-cancer immunotherapy. With the increasing use of PD-1/PD-L1 and CTLA-4 inhibitors, particularly in combination in melanoma and other cancers, timely and accurate diagnosis of colitis will become increasingly important for oncologists. The main goal of this study is to understand the clinical presentation of ipilimumab-induced colitis and to validate the use of CT scans as a safe and effective diagnostic tool. We analyzed a cohort of 303 patients who received ipilimumab at Dana Farber Cancer Institute on an expanded access protocol or standard of care between the years of 2008 and 2015. Age, number of doses and frequency of ipilimumab doses were found to be clinical characteristics which could help differentiate patients who develop ipilimumab induced colitis from those who only present with diarrhea and other gastrointestinal symptoms. Of the 303 patients, 100 (33%) developed diarrhea and 43 (14%) received treatment with corticosteroids for ipilimumab-induced colitis. For all patients with suspected immune-related colitis, an effort was made to firmly establish the diagnosis prior to or immediately after initiation of treatment. Forty-one of 43 patients (95%) who received steroids for presumed immune-related colitis had a colonoscopy and 27 of 43 (63%) patients had both computed tomography (CT) of the abdomen/pelvis and a colonoscopy including biopsy. In the 31 patients with a CT and biopsy, CT was highly predictive of the presence of colitis on biopsy (sensitivity 85%, specificity 75%, PPV 96%) and the absence of CT findings was predictive of a negative biopsy (negative LR 0.2). In the 44 patients who had symptoms and CT evaluation, CT was highly predictive of the need for steroids to reach resolution of symptoms (sensitivity 85%, specificity 88%, PPV 92%, positive LR 7.3). Fifteen of the 17 patients with negative CT findings did not require steroids to reach resolution of symptoms. In conclusion, CT of the abdomen/pelvis is a fast, reliable, and non-invasive mode of diagnosing ipilimumab-induced immune-related colitis, whereas colonoscopy may not be needed to firmly establish that diagnosis

Subjects/Keywords: Medicine; Colonoscopy; CT; Melanoma; Checkpoint blockade; Immune therapy

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APA (6^th Edition):

Garcia-Neuer, M. (2016). Systematic diagnostic evaluation for immune-related colitis: a single institutional review of advanced melanoma patients treated with ipilimumab. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/17019

Chicago Manual of Style (16^th Edition):

Garcia-Neuer, Marlene. “Systematic diagnostic evaluation for immune-related colitis: a single institutional review of advanced melanoma patients treated with ipilimumab.” 2016. Masters Thesis, Boston University. Accessed January 16, 2021. http://hdl.handle.net/2144/17019.

MLA Handbook (7^th Edition):

Garcia-Neuer, Marlene. “Systematic diagnostic evaluation for immune-related colitis: a single institutional review of advanced melanoma patients treated with ipilimumab.” 2016. Web. 16 Jan 2021.

Vancouver:

Garcia-Neuer M. Systematic diagnostic evaluation for immune-related colitis: a single institutional review of advanced melanoma patients treated with ipilimumab. [Internet] [Masters thesis]. Boston University; 2016. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2144/17019.

Council of Science Editors:

Garcia-Neuer M. Systematic diagnostic evaluation for immune-related colitis: a single institutional review of advanced melanoma patients treated with ipilimumab. [Masters Thesis]. Boston University; 2016. Available from: http://hdl.handle.net/2144/17019

University of Cincinnati

7. Furnish, Robin. Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma.

Degree: MS, Pharmacy: Pharmaceutical Sciences, 2020, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532

► Diffuse intrinsic pontine glioma (DIPG) is a rare and lethal pediatric brain tumor arising in?the?midline structures of the brain, namely the pons and thalamus. Surgery… (more)

Subjects/Keywords: Pharmaceuticals; DIPG; CDK4 6; Immune Checkpoint Inhibitor; CDK 4 6 inhibitor

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APA (6^th Edition):

Furnish, R. (2020). Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma. (Masters Thesis). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532

Chicago Manual of Style (16^th Edition):

Furnish, Robin. “Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma.” 2020. Masters Thesis, University of Cincinnati. Accessed January 16, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532.

MLA Handbook (7^th Edition):

Furnish, Robin. “Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma.” 2020. Web. 16 Jan 2021.

Vancouver:

Furnish R. Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma. [Internet] [Masters thesis]. University of Cincinnati; 2020. [cited 2021 Jan 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532.

Council of Science Editors:

Furnish R. Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma. [Masters Thesis]. University of Cincinnati; 2020. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532

Duke University

8. Woroniecka, Karolina. T Cell Exhaustion in Glioblastoma .

Degree: 2020, Duke University

URL: http://hdl.handle.net/10161/20843

► Glioblastoma (GBM) is the most common primary malignant brain tumor. Despite standard of care treatment GBM remains universally lethal, demonstrating a significant need for… (more)

Subjects/Keywords: Oncology; Immunology; Neurosciences; Glioblastoma; Immune Checkpoint Blockade; T Cell Exhaustion

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Woroniecka, K. (2020). T Cell Exhaustion in Glioblastoma . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/20843

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Woroniecka, Karolina. “T Cell Exhaustion in Glioblastoma .” 2020. Thesis, Duke University. Accessed January 16, 2021. http://hdl.handle.net/10161/20843.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Woroniecka, Karolina. “T Cell Exhaustion in Glioblastoma .” 2020. Web. 16 Jan 2021.

Vancouver:

Woroniecka K. T Cell Exhaustion in Glioblastoma . [Internet] [Thesis]. Duke University; 2020. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10161/20843.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Woroniecka K. T Cell Exhaustion in Glioblastoma . [Thesis]. Duke University; 2020. Available from: http://hdl.handle.net/10161/20843

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

9. Jiao, Shiping. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression.

Degree: MS, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/739

► With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition,… (more)

Subjects/Keywords: Cancer Immunotherapy; immune checkpoint; PARP inhibitor; Combination therapy; Cancer Biology; Medical Immunology; Neoplasms; Oncology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jiao, S. (2017). PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. (Thesis). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/739

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jiao, Shiping. “PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression.” 2017. Thesis, Texas Medical Center. Accessed January 16, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/739.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jiao, Shiping. “PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression.” 2017. Web. 16 Jan 2021.

Vancouver:

Jiao S. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. [Internet] [Thesis]. Texas Medical Center; 2017. [cited 2021 Jan 16]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/739.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jiao S. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. [Thesis]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/739

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Western Ontario

10. El-Hajjar, Mikal. Inducing DNA-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity.

Degree: 2020, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/7432

► Immunotherapy has improved patient outcomes in advanced or metastatic settings across a number of cancers. Patients with tumours deficient in the DNA mismatch repair (DNA-MMR)… (more)

Subjects/Keywords: Cancer; DNA-MMR Repair; Immunotherapy; Immune checkpoint inhibitors; MLH1; T-cells; Immunity

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APA (6^th Edition):

El-Hajjar, M. (2020). Inducing DNA-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/7432

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

El-Hajjar, Mikal. “Inducing DNA-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity.” 2020. Thesis, University of Western Ontario. Accessed January 16, 2021. https://ir.lib.uwo.ca/etd/7432.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

El-Hajjar, Mikal. “Inducing DNA-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity.” 2020. Web. 16 Jan 2021.

Vancouver:

El-Hajjar M. Inducing DNA-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity. [Internet] [Thesis]. University of Western Ontario; 2020. [cited 2021 Jan 16]. Available from: https://ir.lib.uwo.ca/etd/7432.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

El-Hajjar M. Inducing DNA-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity. [Thesis]. University of Western Ontario; 2020. Available from: https://ir.lib.uwo.ca/etd/7432

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of South Florida

11. Sodre De Castro Laino, Andressa. Targeting Histone Deacetylases in Melanoma and T-cells to Improve Cancer Immunotherapy.

Degree: 2016, University of South Florida

URL: https://scholarcommons.usf.edu/etd/6144

► Histone deacetylases (HDACs) are key mediators of gene expression and, thus, major regulators of cell function. As such, HDACs play a role in orchestrating tumor… (more)

▼ Histone deacetylases (HDACs) are key mediators of gene expression and, thus, major regulators of cell function. As such, HDACs play a role in orchestrating tumor biology, and the use of small inhibitors targeting theses proteins is attractive for the field of cancer therapy. Indeed, several HDAC inhibitors have received FDA-approval for the treatment of malignancies, while a myriad of these compounds continue to be evaluated in clinical trials. Besides their direct impact on tumor growth, HDAC inhibitors have been shown to increase immunogenicity of cancer cells, facilitating generation of a productive immune response against tumors. Immunotherapeutic approaches take advantage of the intrinsic ability of the immune system to manifest an anti-tumor response. Mechanisms of immune escape are often developed by cancer cells, neutralizing activity of the immune system. For example, upregulation of the PD1 ligands PDL1 and PDL2 by tumor cells negatively regulates the anti-tumor functions of PD1-expressing infiltrating T-cells. Importantly, strategies targeting this inhibitory axis have shown outstanding clinical benefit for the treatment of solid and hematological malignancies. The mechanisms by which HDAC inhibitors modulate tumor and immune cells biology were explored herein. Initially, treatment of melanoma cells with pan- and class I-selective HDAC inhibitors resulted in upregulation of PDL1 and PDL2 molecules. These effects were observed in mouse and human cell lines, as well as in tumor cells resected from metastatic melanoma patients. This upregulation was robust and sustained, lasting at least 96 hours in vitro, and validated in vivo using a B16F10 syngeneic mouse model. Enhanced expression of PDL1 mediated by HDAC inhibitors was found to result from enhanced histone acetylation at the PDL1 gene promoter region. Combination therapy of HDAC inhibition and PD1 blockade was explored in the tumor setting, leading to synergistic effects in terms of reducing melanoma progression and increasing survival of B16F10 melanoma-bearing mice. These data provide a clinical rationale for combination therapy of epigenetic modifiers (e.g. HDAC inhibitors) and PD1 blockade as means to augment cancer immunotherapy, improving patient outcomes. As a second pillar of this research, the impacts of HDAC-selective inhibition were explored on immune cell biology, since the broad nature of pan-HDAC inhibitors was shown to be detrimental to T-cells in vitro and in vivo. Based on screening assay results, novel implications of treating melanoma patient T-cells ex vivo with the HDAC6-selective inhibitor ACY1215 were investigated. Treatment with this compound was unique among pan- and isotype-selective HDAC inhibitors in modulating T-cell cytokine production and showing minimal impact of T-cell viability. ACY1215 tempered Th2 cytokine production (i.e. IL-4, IL-6 and IL-10), and maintained Th1 effector cytokines (e.g. IFNγ and IL-2). Furthermore, ACY1215 increased expression of surface markers, including CD69 activation marker and ICOS…

Subjects/Keywords: HDACs; HDAC Inhibitors; Lymphocytes; Immune Checkpoint Blockade; Immunology and Infectious Disease; Oncology

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APA (6^th Edition):

Sodre De Castro Laino, A. (2016). Targeting Histone Deacetylases in Melanoma and T-cells to Improve Cancer Immunotherapy. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/6144

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sodre De Castro Laino, Andressa. “Targeting Histone Deacetylases in Melanoma and T-cells to Improve Cancer Immunotherapy.” 2016. Thesis, University of South Florida. Accessed January 16, 2021. https://scholarcommons.usf.edu/etd/6144.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sodre De Castro Laino, Andressa. “Targeting Histone Deacetylases in Melanoma and T-cells to Improve Cancer Immunotherapy.” 2016. Web. 16 Jan 2021.

Vancouver:

Sodre De Castro Laino A. Targeting Histone Deacetylases in Melanoma and T-cells to Improve Cancer Immunotherapy. [Internet] [Thesis]. University of South Florida; 2016. [cited 2021 Jan 16]. Available from: https://scholarcommons.usf.edu/etd/6144.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sodre De Castro Laino A. Targeting Histone Deacetylases in Melanoma and T-cells to Improve Cancer Immunotherapy. [Thesis]. University of South Florida; 2016. Available from: https://scholarcommons.usf.edu/etd/6144

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Helsinki

12. Lee, Moon Hee. Characterizing the Immune Phenotype of Tumor Infiltrating Lymphocytes in Renal Cell Carcinoma.

Degree: Medicinska fakulteten, 2017, University of Helsinki

URL: http://hdl.handle.net/10138/191279

► Cancer immunotherapy has advanced with the introduction of anti-PD-1 therapy. Anti-PD-1 therapy blocks the inhibitory immune checkpoint receptor PD-1, and allows T cells to regain… (more)

Subjects/Keywords: RCC; TILs; renal cell carcinoma; NK cell; immune checkpoint; tumor infiltrating lymphocytes; Cancer immunology

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APA (6^th Edition):

Lee, M. H. (2017). Characterizing the Immune Phenotype of Tumor Infiltrating Lymphocytes in Renal Cell Carcinoma. (Masters Thesis). University of Helsinki. Retrieved from http://hdl.handle.net/10138/191279

Chicago Manual of Style (16^th Edition):

Lee, Moon Hee. “Characterizing the Immune Phenotype of Tumor Infiltrating Lymphocytes in Renal Cell Carcinoma.” 2017. Masters Thesis, University of Helsinki. Accessed January 16, 2021. http://hdl.handle.net/10138/191279.

MLA Handbook (7^th Edition):

Lee, Moon Hee. “Characterizing the Immune Phenotype of Tumor Infiltrating Lymphocytes in Renal Cell Carcinoma.” 2017. Web. 16 Jan 2021.

Vancouver:

Lee MH. Characterizing the Immune Phenotype of Tumor Infiltrating Lymphocytes in Renal Cell Carcinoma. [Internet] [Masters thesis]. University of Helsinki; 2017. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10138/191279.

Council of Science Editors:

Lee MH. Characterizing the Immune Phenotype of Tumor Infiltrating Lymphocytes in Renal Cell Carcinoma. [Masters Thesis]. University of Helsinki; 2017. Available from: http://hdl.handle.net/10138/191279

Freie Universität Berlin

13. Strauch, Nicole. Evaluation of Psychosocial Factors and Patient Competence of the Management of Side Effects of Cancer Patients Undergoing Immune-Checkpoint-Inhibitor-Therapy.

Degree: 2020, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-27286

► Introduction Immune checkpoint inhibitors (ICI) have led to significant change of cancer therapy but are associated with immunrelated adverse events which need regular assessment and… (more)

▼ Introduction Immune checkpoint inhibitors (ICI) have led to significant change of cancer therapy but are associated with immunrelated adverse events which need regular assessment and prompt treatment. The implementation into standard cancer therapy is associated with new challenges for all persons involved. Aims of this study were to identify specific needs and psycho-social burden of patients and to define specific interventions in order to increase patient’s health related quality of life and adherence related to side-effects management and to evaluate patient competency. Methods In a qualitative Interview-study 14 patients of different cancer entities, all undergoing ICI therapy were included. Semi-structured interviews were conducted and a questionnaire for patient competency was completed. Results were analyzed via evaluative, type-building content analysis and analysis of the questionnaires. Results Data shows that the subjectively perceived psycho-social burden results from long patient journeys, fear of death, loss of quality of life, missing social support, lack of information regarding the treatment, and a missing self-conception of co-determination rights. However, patients report satisfaction with fewer therapy-associated side-effects. The patients have strong belief in oncological care and the decisions of the physicians. Yet the feeling of not being sufficiently informed and seeing themselves as medical laymen was perceived a distinct burden. It seems like there is a mental blockade of collecting information. A reason for that might be found in the fear of discontinuation of therapy. To be able to deal better with this anxiety patients repress information. There were low to mean values for patient competency. Conclusions To ensure that both adherence to side-effects management and high quality of life is maintained, therapy-specific training should be offered to patients. Information sharing should focus on a comprehensive, patient-oriented language and method of presentation. To increase self-efficacy in patients, non-physician professionals may also present the information additionally to the physicians. Training by nurses, psychologists, or moderated patient groups may be a meaningful supplement. Introducing patients to specific scientific validated apps or websites might be a useful addition since these would be continuously available. Since physicians play a crucial role for patients, physicians should introduce such additional information sources. Advisors/Committee Members: female (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: Immune-Checkpoint-Inhibitor-Therapy; Cancer; Psychooncology; irAEs; Psychosocial Factors; Patient Competence; ddc:610

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APA (6^th Edition):

Strauch, N. (2020). Evaluation of Psychosocial Factors and Patient Competence of the Management of Side Effects of Cancer Patients Undergoing Immune-Checkpoint-Inhibitor-Therapy. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-27286

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Strauch, Nicole. “Evaluation of Psychosocial Factors and Patient Competence of the Management of Side Effects of Cancer Patients Undergoing Immune-Checkpoint-Inhibitor-Therapy.” 2020. Thesis, Freie Universität Berlin. Accessed January 16, 2021. http://dx.doi.org/10.17169/refubium-27286.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Strauch, Nicole. “Evaluation of Psychosocial Factors and Patient Competence of the Management of Side Effects of Cancer Patients Undergoing Immune-Checkpoint-Inhibitor-Therapy.” 2020. Web. 16 Jan 2021.

Vancouver:

Strauch N. Evaluation of Psychosocial Factors and Patient Competence of the Management of Side Effects of Cancer Patients Undergoing Immune-Checkpoint-Inhibitor-Therapy. [Internet] [Thesis]. Freie Universität Berlin; 2020. [cited 2021 Jan 16]. Available from: http://dx.doi.org/10.17169/refubium-27286.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Strauch N. Evaluation of Psychosocial Factors and Patient Competence of the Management of Side Effects of Cancer Patients Undergoing Immune-Checkpoint-Inhibitor-Therapy. [Thesis]. Freie Universität Berlin; 2020. Available from: http://dx.doi.org/10.17169/refubium-27286

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

14. McGuire, Michael. INVESTIGATING THE IMPACT OF INTRAGENIC DNA METHYLATION ON GENE EXPRESSION, AND THE CLINICAL IMPLICATIONS ON TUMOR CELLS AND ASSOCIATED STROMA.

Degree: PhD, 2018, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/852

► Investigations into the function of non-promoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance… (more)

▼ Investigations into the function of non-promoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance of distinguishing between DNA methylation in discrete functional regions; however, integrated non-promoter DNA methylation and gene expression analyses across a wide number of tumor types and corresponding normal tissues have not been performed. Through integrated analysis of gene expression and DNA methylation profiles, we uncovered an enrichment of DNA methylation sites within the gene body and 3’UTR in which DNA methylation is strongly positively correlated with gene expression. We examined 32 tumor types and identified 57 tumor suppressors and oncogenes out of 224 genes containing a correlation of > 0.5 between gene body methylation and gene expression in at least 1 tumor type. The lymphocyte-specific gene CARD11 exhibits robust association between gene body methylation and expression across 19 of 32 tumor types examined. It is significantly overexpressed in KIRC and LUAD, and has a z-score of 4 in KIRC, meaning that high expression of CARD11 in this tumor type was associated with lower patient overall survival. Contrary to its canonical function in lymphocyte NF-kB activation, CARD11 activates the mTOR pathway in KIRC and LUAD, resulting in suppressed autophagy, and demethylation of a CpG island within the gene body of CARD11 decreases gene expression. In addition to methylation of the open reading frame portion of a gene, other regions of site-specific DNA methylation along the gene body remain to be explored. Upon segregating the gene body into discrete functional units (5’UTR, 1^st exon, 3’UTR), it was noted that the 3’UTR contained an enrichment of probes positively correlated between DNA methylation and gene expression. In 5 of 10 tumor types examined, DNA methylation of the 3’UTR is associated with patient survival in a significant number of genes. Filtering for genes in which 3’UTR DNA methylation, relative to gene body DNA methylation, is more strongly correlated with gene expression yields a list of 156 genes, enriched for functions involving T cell activation. Activating T cells ex vivo caused the immune checkpoint gene HAVCR2, but not other genes examined, to show a substantial increase in 3’UTR DNA methylation, but not adjacent exonic/intronic, or promoter DNA methylation, upon upregulation of gene expression. Furthermore, this increase in HAVCR2 gene expression can be abrogated by treatment with demethylating agents. These findings implicate the 3’UTR as a functionally relevant DNA methylation site, particularly regarding T cell activity. Additionally, they reveal a novel mechanism by which HAVCR2 is upregulated in T cells, providing a new molecular target for immune checkpoint blockade. Advisors/Committee Members: Anil Sood, Menashe Bar-Eli, Sharon Dent.

Subjects/Keywords: 3'UTR; DNA methylation; T cells; Immune checkpoint; Bioinformatics; Medicine and Health Sciences; Molecular Biology; Molecular Genetics

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APA (6^th Edition):

McGuire, M. (2018). INVESTIGATING THE IMPACT OF INTRAGENIC DNA METHYLATION ON GENE EXPRESSION, AND THE CLINICAL IMPLICATIONS ON TUMOR CELLS AND ASSOCIATED STROMA. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/852

Chicago Manual of Style (16^th Edition):

McGuire, Michael. “INVESTIGATING THE IMPACT OF INTRAGENIC DNA METHYLATION ON GENE EXPRESSION, AND THE CLINICAL IMPLICATIONS ON TUMOR CELLS AND ASSOCIATED STROMA.” 2018. Doctoral Dissertation, Texas Medical Center. Accessed January 16, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/852.

MLA Handbook (7^th Edition):

McGuire, Michael. “INVESTIGATING THE IMPACT OF INTRAGENIC DNA METHYLATION ON GENE EXPRESSION, AND THE CLINICAL IMPLICATIONS ON TUMOR CELLS AND ASSOCIATED STROMA.” 2018. Web. 16 Jan 2021.

Vancouver:

McGuire M. INVESTIGATING THE IMPACT OF INTRAGENIC DNA METHYLATION ON GENE EXPRESSION, AND THE CLINICAL IMPLICATIONS ON TUMOR CELLS AND ASSOCIATED STROMA. [Internet] [Doctoral dissertation]. Texas Medical Center; 2018. [cited 2021 Jan 16]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/852.

Council of Science Editors:

McGuire M. INVESTIGATING THE IMPACT OF INTRAGENIC DNA METHYLATION ON GENE EXPRESSION, AND THE CLINICAL IMPLICATIONS ON TUMOR CELLS AND ASSOCIATED STROMA. [Doctoral Dissertation]. Texas Medical Center; 2018. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/852

15. D'Almeida, Sénan. Rôle de l’éctonucléotidase CD39 dans l’acquisition d’un phénotype immunorégulateur par les macrophages associés aux tumeurs : The ectonucleotidase CD39 in the acquisition of an immunosuppressive phenotype by tumor-associated macrophages.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2015, Angers

URL: http://www.theses.fr/2015ANGE0006

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Les macrophages associés aux tumeurs (TAM) sont des cellules immunorégulatrices qui s’accumulent massivement dans le microenvironnement (ME) tumoral. Chez les patients atteints de cancer de… (more)

▼

Les macrophages associés aux tumeurs (TAM) sont des cellules immunorégulatrices qui s’accumulent massivement dans le microenvironnement (ME) tumoral. Chez les patients atteints de cancer de l’ovaire (CO) ou de mésothéliome pleural malin (MPM), leur densité est associé à un mauvais pronostic. Le projet est porté sur la caractérisation des mécanismes impliqués dans leur recrutement et leur polarisation. L’éctonucléotidase CD39 hydrolyse l’ATP enadénosine extracellulaire, présentant des propriétés immunosuppressives. Nous avons montré que les TAMCD14+CD163+ isolés de CO et les M générés in vitro en présence de M-CSF, expriment un niveau élevé de CD39membranaire comparativement aux M immunostimulants. L’inhibition de CD39 diminue les fonctions immunorégulatrices des M CD163+CD39+high (i.e. IL-10 etPD-L1). Nous avons identifié la cytokine IL-27, sécrétée parles neutrophiles infiltrants la tumeur, comme rhéostat de l’expression de CD39. En conséquence, neutraliser l’IL-27pendant la différenciation des M en présence de M-CSF diminue l’expression de CD39 et PD-L1 ainsi que la sécrétiond’IL-10 par ces M . Parallèlement, nous avons montré que les effusions pleurales du MPM induisent la migration des monocytes via CCL2, polarisent les monocytes en MCD163+ et protègent des cellules tumorales de l’effet des agents cytotoxiques. L’ensemble de ces résultats suggère que le ciblage du recrutement (CCL2) et des molécules impliquées dans la polarisation des TAM (ligands du MCSFR,IL-27, CD39) représentent de nouvelles pistes thérapeutiques dans le traitement de certaines tumeurs solides.

Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment (ME). In patients with ovarian cancer (OC) and malignant pleural mesothelioma (MPM), their density is correlated with poor prognosis. Targeting mediators that control the recruitment or the polarization of immunoregulatory macrophages (M ) represents therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties. We report here thatCD14+CD163+ TAM isolated from OC patients and Mgenerated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated M . CD39 blockade diminished some of the immunosuppressive functions ofCD163+CD39hugh, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumorin-filtrating neutrophils, located close to infiltratingCD163+ M , as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 down-regulatedCD39, PD-L1 expression as well as IL-10 secretion byM-CSF-M . In parallel, we showed that pleural effusion of MPM induced monocytes migration via CCL2, the polarization of monocytes into CD163+ and induced protection to tumor cell death after chemotherapeutic treatments. Collectively, these data suggest that…

Advisors/Committee Members: Delneste, Yves (thesis director).

Subjects/Keywords: NTPDase1 CD39; Immunorégulation; Points de contrôles immunologiques (PD-L1); NTPDase1 CD39; Immunoregulation; Immune checkpoint (PD-L1); 610

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

D'Almeida, S. (2015). Rôle de l’éctonucléotidase CD39 dans l’acquisition d’un phénotype immunorégulateur par les macrophages associés aux tumeurs : The ectonucleotidase CD39 in the acquisition of an immunosuppressive phenotype by tumor-associated macrophages. (Doctoral Dissertation). Angers. Retrieved from http://www.theses.fr/2015ANGE0006

Chicago Manual of Style (16^th Edition):

D'Almeida, Sénan. “Rôle de l’éctonucléotidase CD39 dans l’acquisition d’un phénotype immunorégulateur par les macrophages associés aux tumeurs : The ectonucleotidase CD39 in the acquisition of an immunosuppressive phenotype by tumor-associated macrophages.” 2015. Doctoral Dissertation, Angers. Accessed January 16, 2021. http://www.theses.fr/2015ANGE0006.

MLA Handbook (7^th Edition):

D'Almeida, Sénan. “Rôle de l’éctonucléotidase CD39 dans l’acquisition d’un phénotype immunorégulateur par les macrophages associés aux tumeurs : The ectonucleotidase CD39 in the acquisition of an immunosuppressive phenotype by tumor-associated macrophages.” 2015. Web. 16 Jan 2021.

Vancouver:

D'Almeida S. Rôle de l’éctonucléotidase CD39 dans l’acquisition d’un phénotype immunorégulateur par les macrophages associés aux tumeurs : The ectonucleotidase CD39 in the acquisition of an immunosuppressive phenotype by tumor-associated macrophages. [Internet] [Doctoral dissertation]. Angers; 2015. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2015ANGE0006.

Council of Science Editors:

D'Almeida S. Rôle de l’éctonucléotidase CD39 dans l’acquisition d’un phénotype immunorégulateur par les macrophages associés aux tumeurs : The ectonucleotidase CD39 in the acquisition of an immunosuppressive phenotype by tumor-associated macrophages. [Doctoral Dissertation]. Angers; 2015. Available from: http://www.theses.fr/2015ANGE0006

16. Shekarian, Tala. Immunostimulatory and Oncolytic Properties of Rotavirus Can Overcome Resistance to Immune Checkpoint Blockade Therapy : Voie de signalisation de TLR4 et Rig I dans le neuroblastome : rôle biologique, valeur pronostique et utilisation dans les thérapeutique ciblées.

Degree: Docteur es, Immuno-oncologie, 2017, Lyon

URL: http://www.theses.fr/2017LYSE1048

►

L'apport des anticorps immunomodulateurs ciblant PD-1, PD-L1 et CTLA-4 ont récemment révolutionné la prise en charge thérapeutique du cancer. Cependant, seule une minorité de patients… (more)

▼

L'apport des anticorps immunomodulateurs ciblant PD-1, PD-L1 et CTLA-4 ont récemment révolutionné la prise en charge thérapeutique du cancer. Cependant, seule une minorité de patients développent des réponses objectives à ces traitements. Par conséquent, de nouvelles innovation thérapeutiques sont nécessaires afin d'augmenter l'immunogénicité des tumeurs et de surmonter la résistance à la thérapie contre les anticorps immunomodulateurs. Les propriétés oncolytiques de certains virus peuvent être exploitées afin de permettre un amorçage de l'immunité anti-tumorale. Différents virus oncolytiques (OVS) sont actuellement en développement clinique intense en combinaison avec des thérapies par anticorps immunomodulateurs. Nous avons trouvé qu'un vaccin viral pédiatrique disponible dans le commerce a des propriétés oncolytiques. Ce virus pédiatrique peut tuer directement les cellules cancéreuses, avec des caractéristiques de mort cellulaire immunogène. De plus, ce virus a des propriétés pro-inflammatoires et peut activer la voie NF-kB indépendamment des voies de danger cellulaire (TLR et IRF). Ces propriétés biologiques in vitro se traduisent in vivo en une activité anti-tumorale. L'Injection intra-tumorale du vaccin a des effets anti-tumoraux directs mais également à médiation immunitaire. De façon intéressante, dans des modèles de souris immunocompétentes porteuses de tumeurs murines, l'injection intra-tumorale de vaccin a un effet synergique avec des anti CTLA-4 permettant la guérison de 100% des souris. Les vaccins sont des produits pédiatriques et adultes de grade clinique. Par conséquent, des stratégies de vaccination in situ par injection intra-tumorale pourraient être rapidement mises en clinique

Immune checkpoint targeted therapies against PD-1, PD-L1 and CTLA-4 are currently revolutionizing cancer care. However, only a minority of patients develop objective responses with these treatments. Therefore, new therapeutic interventions are needed to increase the immunogenicity of tumors in order to overcome resistance to immune checkpoint blockade therapy. Oncolytic properties of common viruses can be exploited for the priming of anti-tumor immunity and such oncolytic viruses (OVs) are currently in intense clinical development in combination with immune checkpoint targeted therapies. We have found that commercially available virus vaccines do have oncolytic properties. These pediatric vaccine virus can directly kill cancer cells with features of immunogenic cell death. Moreover, it has pro-inflammatory properties and can activate the NF-Kb pathway in a toll-like receptor and IRF3 independent manner. These in vitro biological properties translate in vivo into anti-tumor activity. Intra-tumoral vaccine therapy has anti-tumor effects which are partly immune mediated. Interestingly, in immunocompetent murine pediatric tumor models, intra-tumoral injection overcome resistance and synergize with immune checkpoint targeted therapy. Vaccines are pediatric and adult clinical grade products. Therefore, in situ intra-tumoral…

Advisors/Committee Members: Caux, Christophe (thesis director).

Subjects/Keywords: Virus oncolytique; Anticorps immunomodulateur; Neuroblastome; Agonistes de PRRs; Oncolytic virus; Immune checkpoint blockade antibodies; Neuroblastoma; PRRs Agonits; 616.99

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shekarian, T. (2017). Immunostimulatory and Oncolytic Properties of Rotavirus Can Overcome Resistance to Immune Checkpoint Blockade Therapy : Voie de signalisation de TLR4 et Rig I dans le neuroblastome : rôle biologique, valeur pronostique et utilisation dans les thérapeutique ciblées. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2017LYSE1048

Chicago Manual of Style (16^th Edition):

Shekarian, Tala. “Immunostimulatory and Oncolytic Properties of Rotavirus Can Overcome Resistance to Immune Checkpoint Blockade Therapy : Voie de signalisation de TLR4 et Rig I dans le neuroblastome : rôle biologique, valeur pronostique et utilisation dans les thérapeutique ciblées.” 2017. Doctoral Dissertation, Lyon. Accessed January 16, 2021. http://www.theses.fr/2017LYSE1048.

MLA Handbook (7^th Edition):

Shekarian, Tala. “Immunostimulatory and Oncolytic Properties of Rotavirus Can Overcome Resistance to Immune Checkpoint Blockade Therapy : Voie de signalisation de TLR4 et Rig I dans le neuroblastome : rôle biologique, valeur pronostique et utilisation dans les thérapeutique ciblées.” 2017. Web. 16 Jan 2021.

Vancouver:

Shekarian T. Immunostimulatory and Oncolytic Properties of Rotavirus Can Overcome Resistance to Immune Checkpoint Blockade Therapy : Voie de signalisation de TLR4 et Rig I dans le neuroblastome : rôle biologique, valeur pronostique et utilisation dans les thérapeutique ciblées. [Internet] [Doctoral dissertation]. Lyon; 2017. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2017LYSE1048.

Council of Science Editors:

Shekarian T. Immunostimulatory and Oncolytic Properties of Rotavirus Can Overcome Resistance to Immune Checkpoint Blockade Therapy : Voie de signalisation de TLR4 et Rig I dans le neuroblastome : rôle biologique, valeur pronostique et utilisation dans les thérapeutique ciblées. [Doctoral Dissertation]. Lyon; 2017. Available from: http://www.theses.fr/2017LYSE1048

University of Gothenburg / Göteborgs Universitet

17. Ahlmanner, Filip. Regulatory T cells and mucosal-associated invariant T cells in colon adenocarcinomas; Phenotype and function.

Degree: 2019, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/58240

► In many solid cancers, and also in colon adenocarcinomas, an increased accumulation of lymphocytes is beneficial for the patient. However, tumor-infiltrating immune cells may be… (more)

▼ In many solid cancers, and also in colon adenocarcinomas, an increased accumulation of lymphocytes is beneficial for the patient. However, tumor-infiltrating immune cells may be either pro- or anti-tumorigenic and the balance between these two counteracting forces partly determines patient outcome. Boosting of the anti-tumor immune response by immunotherapy, e.g. by immune checkpoint blockade, has been highly successful in several types of cancer but less so for colon cancer. In the interest of developing new cancer immunotherapies also for the treatment of colon cancer, additional studies of tumor-infiltrating lymphocytes in colon cancer are warranted. In this study, we used flow cytometry and flow cytometric cell sorting as well as in vitro cell culture assays to examine the phenotype and effector functions of two distinct immune cell populations which we have shown to accumulate in tumors of colon cancer patients, CD39+ regulatory T cells (CD39+ Treg) and mucosal-associated invariant T (MAIT) cells. Treg reduce the activity of other immune cells and can express the surface molecule CD39, an ectoenzyme involved in converting extracellular ATP to immunosuppressive adenosine. MAIT cells recognize bacterial metabolites and are innate-like T cells which are believed to provide a first line defense at epithelial surfaces. This thesis comprises an extensive phenotypic and functional characterization of these two subsets in colon tumors, and also preliminary survival data on their respective impact on patient prognosis. We show that CD39+ Treg constitute a highly activated and immunosuppressive Treg subset. In particular, surface expression of immunomodulatory mediators were increased in the CD39+ Treg subset, while cytokine production was similar in CD39+ and CD39- Treg. We also present preliminary survival data which suggests a correlation between high levels of CD39 expression on intratumoral Treg and a worse patient prognosis, thus highlighting CD39+ Treg as a potential candidate for targeted immunotherapy. With regard to MAIT cells, we could demonstrate accumulation of MAIT cells in colon adenocarcinomas. However, there were reduced frequencies of IFN-gamma-producing cells among tumor-associated MAIT cells compared to MAIT cells from unaffected colon tissue. MAIT-cell infiltration into colon tumors has been correlated with poor patient prognosis and in an independent appendix of the thesis, we present preliminary data actually showing a positive impact of MAIT cell infiltration into colon tumors on patient survival.

Subjects/Keywords: colon cancer; regulatory T cells; CD39; adenosine; immune checkpoint molecules; immunosuppression; MAIT cells; cytokines; cancer-specific survival

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ahlmanner, F. (2019). Regulatory T cells and mucosal-associated invariant T cells in colon adenocarcinomas; Phenotype and function. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/58240

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ahlmanner, Filip. “Regulatory T cells and mucosal-associated invariant T cells in colon adenocarcinomas; Phenotype and function.” 2019. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed January 16, 2021. http://hdl.handle.net/2077/58240.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ahlmanner, Filip. “Regulatory T cells and mucosal-associated invariant T cells in colon adenocarcinomas; Phenotype and function.” 2019. Web. 16 Jan 2021.

Vancouver:

Ahlmanner F. Regulatory T cells and mucosal-associated invariant T cells in colon adenocarcinomas; Phenotype and function. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2019. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2077/58240.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ahlmanner F. Regulatory T cells and mucosal-associated invariant T cells in colon adenocarcinomas; Phenotype and function. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2019. Available from: http://hdl.handle.net/2077/58240

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Victoria

18. Hanley, Ronan. Inhibitors of the PD1/PD-L1 interaction: missteps, mechanisms and mysteries.

Degree: Department of Chemistry, 2018, University of Victoria

URL: https://dspace.library.uvic.ca//handle/1828/9136

► The interactions of tumours with normal host tissue are key determinants of cancer growth and progression. The ability or inability of the patient’s immune system… (more)

▼ The interactions of tumours with normal host tissue are key determinants of cancer growth and progression. The ability or inability of the patient’s immune system to mount a response against the tumour is tightly correlated with prognosis. One of the ways tumours avoid detection and elimination by the immune system is by expressing programmed death ligand 1 (PD-L1). PD-L1 binds to its receptor programmed death 1 (PD1) on T cells, inhibiting T cell responsiveness to antigenic stimuli. Blockade of the PD1/PD-L1 pathway removes this negative signal and restores anti-tumour immunity. While this blockade of PD1/PD-L1 is well established through the use of antibodies, small molecule inhibitors of PD1/PD-L1 are relatively unknown. We employed in silico docking in order to find small molecules capable of binding to either PD1 or PD-L1, and the highest-ranked compounds were tested in biophysical assays for their ability to inhibit PD1/PD-L1 binding. A thermal shift assay identified a pyrazole compound as a possible binding partner for PD-L1, but follow-up assays showed that it had no effect on the PD1/PD-L1 interaction and that its apparent binding was probably due to aggregation. An ELISA assay identified a tryptophan diamine compound as an apparent stabilizer of the PD1/PD-L1 interaction. However this compound, too, was later identified to be inactive in orthogonal assays. We identified a family of salicylic acid derivatives that interfered with TR-FRET measurements – an unusual observation, given that TR-FRET is touted as being insensitive to most mechanisms of compound interference. This discovery should help other fragment- screening groups identify false positives more easily. We also probed the mechanism of inhibition of a recently disclosed family of small molecule PD1/PD-L1 inhibitors from Bristol-Myers Squibb. Concurrently with other groups, we used protein NMR, size exclusion chromatography, and SPR to determine that the compounds were inducing homodimerization through the PD1-binding face of PD-L1. Furthermore, using cellular crosslinking and live cell imaging, we showed that these first generation inhibitors are fairly ineffective at inhibiting this interaction on the cell surface. More potent compounds will be needed to see any cellular effect from this mechanism of action. Advisors/Committee Members: Hof, Fraser Alan (supervisor), Wulff, Jeremy Earle (supervisor).

Subjects/Keywords: chemical biology; immunology; oncology; immune checkpoint; programmed death 1; PD1; PDL1; programmed death ligand 1; assay interference

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hanley, R. (2018). Inhibitors of the PD1/PD-L1 interaction: missteps, mechanisms and mysteries. (Thesis). University of Victoria. Retrieved from https://dspace.library.uvic.ca//handle/1828/9136

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hanley, Ronan. “Inhibitors of the PD1/PD-L1 interaction: missteps, mechanisms and mysteries.” 2018. Thesis, University of Victoria. Accessed January 16, 2021. https://dspace.library.uvic.ca//handle/1828/9136.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hanley, Ronan. “Inhibitors of the PD1/PD-L1 interaction: missteps, mechanisms and mysteries.” 2018. Web. 16 Jan 2021.

Vancouver:

Hanley R. Inhibitors of the PD1/PD-L1 interaction: missteps, mechanisms and mysteries. [Internet] [Thesis]. University of Victoria; 2018. [cited 2021 Jan 16]. Available from: https://dspace.library.uvic.ca//handle/1828/9136.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hanley R. Inhibitors of the PD1/PD-L1 interaction: missteps, mechanisms and mysteries. [Thesis]. University of Victoria; 2018. Available from: https://dspace.library.uvic.ca//handle/1828/9136

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

19. TAY CHIN KANG JOHAN. IMMUNOTHERAPY AGAINST ADVANCED CANCERS – CHIMERIC ANTIGEN RECEPTOR-BASED APPROACH AND IMMUNE CHECKPOINT REGULATION.

Degree: 2019, National University of Singapore

URL: https://scholarbank.nus.edu.sg/handle/10635/154169

Subjects/Keywords: CAR; CSR; NGK2D; immune checkpoint; cancer immunotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

JOHAN, T. C. K. (2019). IMMUNOTHERAPY AGAINST ADVANCED CANCERS – CHIMERIC ANTIGEN RECEPTOR-BASED APPROACH AND IMMUNE CHECKPOINT REGULATION. (Thesis). National University of Singapore. Retrieved from https://scholarbank.nus.edu.sg/handle/10635/154169

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

JOHAN, TAY CHIN KANG. “IMMUNOTHERAPY AGAINST ADVANCED CANCERS – CHIMERIC ANTIGEN RECEPTOR-BASED APPROACH AND IMMUNE CHECKPOINT REGULATION.” 2019. Thesis, National University of Singapore. Accessed January 16, 2021. https://scholarbank.nus.edu.sg/handle/10635/154169.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

JOHAN, TAY CHIN KANG. “IMMUNOTHERAPY AGAINST ADVANCED CANCERS – CHIMERIC ANTIGEN RECEPTOR-BASED APPROACH AND IMMUNE CHECKPOINT REGULATION.” 2019. Web. 16 Jan 2021.

Vancouver:

JOHAN TCK. IMMUNOTHERAPY AGAINST ADVANCED CANCERS – CHIMERIC ANTIGEN RECEPTOR-BASED APPROACH AND IMMUNE CHECKPOINT REGULATION. [Internet] [Thesis]. National University of Singapore; 2019. [cited 2021 Jan 16]. Available from: https://scholarbank.nus.edu.sg/handle/10635/154169.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

JOHAN TCK. IMMUNOTHERAPY AGAINST ADVANCED CANCERS – CHIMERIC ANTIGEN RECEPTOR-BASED APPROACH AND IMMUNE CHECKPOINT REGULATION. [Thesis]. National University of Singapore; 2019. Available from: https://scholarbank.nus.edu.sg/handle/10635/154169

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

20. Reguera Núñez, Elaine. Biologic and Therapeutic Studies to Improve the Anti-tumor Efficacy of Antiangiogenic Tyrosine Kinase Inhibitors.

Degree: PhD, 2019, University of Toronto

URL: http://hdl.handle.net/1807/97030

► Antiangiogenic tyrosine kinase inhibitors (TKIs), unlike VEGF pathway-targeting antibodies, have failed to show meaningful antitumor efficacy in most solid cancer types, even when combined with… (more)

▼ Antiangiogenic tyrosine kinase inhibitors (TKIs), unlike VEGF pathway-targeting antibodies, have failed to show meaningful antitumor efficacy in most solid cancer types, even when combined with standard chemotherapy. The overall goal of the studies undertaken for this thesis was to study various strategies to improve the anti-tumor efficacy of antiangiogenic TKIs that may include mechanisms other than antiangiogenesis, eg. direct tumor cell killing or immunological effects. The conventional daily protocol for the antiangiogenic TKI pazopanib was modified by increasing doses administered intermittently as a possible strategy to overcome intrinsic resistance of VHL-wildtype renal cell carcinoma or advanced metastatic breast cancer. Administering high dose pazopanib intermittently improved efficacy only in the advanced metastatic breast cancer model, suggesting that any benefit may depend on prior sensitivity of the primary tumor to pazopanib. Most of antiangiogenic TKIs have failed to reach primary efficacy endpoints in phase III trials when combined with chemotherapy, in contrast to antiangiogenic antibodies. In a head-to-head comparative study involving two antiangiogenic TKIs (nintedanib, sunitinib), the VEGFR2 antibody DC101, and one chemotherapeutic drug (paclitaxel), I evaluated whether such failures may be related in part to the inability of TKIs to inhibit chemotherapy-induced pro-tumorigenic, host responses, which antiangiogenic antibodies are known to prevent. The difference between antibodies and TKIs in enhancing chemotherapy efficacy seems to be related to their specificity/targets, which impacts the intratumoral immune microenvironment. Based on the results concerning the effects of TKIs on the intratumoral microenvironment, and the local immunosuppressive effect of VEGF, I also tested whether combining nintedanib, and/or paclitaxel with a PD-L1 immune checkpoint antibody, can improve the efficacy of the immunotherapy, using a triple negative breast cancer model. Either nintedanib or paclitaxel can improve the activity of PD-L1 antibody in the primary tumor treatment setting, whereas only the triple combination appears to be more effective when treating metastatic disease. Considering the outcomes of the two strategies tested, and the effect of TKIs on the intratumoral bone marrow-derived immune cells, it appears that the combination of a TKI such as nintedanib with a PD-L1 therapy is a more promising therapeutic option than administering high dose intermittent TKI. Advisors/Committee Members: Kerbel, Robert S, Medical Biophysics.

Subjects/Keywords: antiangiogenic drugs; bone marrow-derived cells; immune checkpoint inhibitor; metastasis; preclinical models; tyrosine kinase inhibitors; 0992

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Reguera Núñez, E. (2019). Biologic and Therapeutic Studies to Improve the Anti-tumor Efficacy of Antiangiogenic Tyrosine Kinase Inhibitors. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/97030

Chicago Manual of Style (16^th Edition):

Reguera Núñez, Elaine. “Biologic and Therapeutic Studies to Improve the Anti-tumor Efficacy of Antiangiogenic Tyrosine Kinase Inhibitors.” 2019. Doctoral Dissertation, University of Toronto. Accessed January 16, 2021. http://hdl.handle.net/1807/97030.

MLA Handbook (7^th Edition):

Reguera Núñez, Elaine. “Biologic and Therapeutic Studies to Improve the Anti-tumor Efficacy of Antiangiogenic Tyrosine Kinase Inhibitors.” 2019. Web. 16 Jan 2021.

Vancouver:

Reguera Núñez E. Biologic and Therapeutic Studies to Improve the Anti-tumor Efficacy of Antiangiogenic Tyrosine Kinase Inhibitors. [Internet] [Doctoral dissertation]. University of Toronto; 2019. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1807/97030.

Council of Science Editors:

Reguera Núñez E. Biologic and Therapeutic Studies to Improve the Anti-tumor Efficacy of Antiangiogenic Tyrosine Kinase Inhibitors. [Doctoral Dissertation]. University of Toronto; 2019. Available from: http://hdl.handle.net/1807/97030

University of South Florida

21. Xie, Mengyu. A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy.

Degree: 2019, University of South Florida

URL: https://scholarcommons.usf.edu/etd/8094

► Despite the recent success of immune-checkpoint blockade therapy for late-stage non-small cell lung cancer (NSCLC), lung cancer is still the leading cause of cancer deaths… (more)

▼ Despite the recent success of immune-checkpoint blockade therapy for late-stage non-small cell lung cancer (NSCLC), lung cancer is still the leading cause of cancer deaths worldwide. One of the most important characteristics of lung cancer in therapeutic decision-making are the targetable molecules, including EGFR, ALK, BRAF, and MEK. The excitement of immune-checkpoint blockade therapy has triggered concerted efforts that focus on exploring combinations of immune checkpoint therapy with other approved therapeutic regimens aiming at further augmenting positive outcomes and survival. However, the lack of understanding of underlying mechanisms and evidence-based clinical testing has hindered the progress to a cure. Hence, the goal of the study presented here is to elucidate the cross-talk between targeted agents and cytokine response pathways in cancer cells. The goal of the first part of this study was to investigate the molecular mechanisms of cancer cells in response to MEK inhibitors (MEKi), through which lung cancer cells are rendered sensitive to TNFα and IFNγ. We found that BRAF inhibitor and MEKi treatment of melanoma patients led to the activation of tumor NF-κB activity. In vitro studies revealed that MEKi potentiate the response to TNFα, a potent activator of NF-κB. In both melanoma and lung cancer cells, MEKi induced a strong increase in the cell surface expression of TNFα receptor 1 (TNFR1), subsequently enhancing NF-κB activation and augmenting the expression of genes regulated by TNFα and IFNγ. Screening of 289 targeted agents for the ability to increase TNFα + IFNγ target gene expression demonstrated that this was a general activity of inhibitors of MEK and ERK kinases. Treatment with MEKi led to the acquisition of a novel vulnerability to TNFα + IFNγ-induced apoptosis in lung cancer cells that were refractory to MEKi killing as well as the augmentation of cell cycle arrest. Lung cancer cell knock-out of TNFR1 impaired the anti-tumor efficacy of MEKi, whereas TNFα + IFNγ administration in MEKi-treated mice enhanced the anti-tumor response. Finally, immunotherapeutics known to induce the expression of these cytokines synergized with MEKi in eradicating tumors. These findings define a novel cytokine response modulatory function of MEKi that can be therapeutically exploited. The second part of this study explored the above-described concept in a more translationally relevant setting. In immune therapies, TNFα and IFNγ are primarily produced by tumor-infiltration lymphocytes (TILs) that are adoptively transferred or reactivated by immune-checkpoint blockade. Whereas activated T cells recognize and eliminate specific antigen-expressing cancer cells, the cytokines secreted by those T cells impact broader targets, including those that are able to escape from direct T cell antigen recognition. This non-specific anti-tumor effect is important for long-term therapeutic response but is currently overlooked and less exploited. To understand the relative contribution of the cytokine mediated killing, an in vitro…

Subjects/Keywords: IFNγ; Immune Checkpoint Blockade; Lung cancer; MEK inhibitors; NF-κB; TNFα; Immunology and Infectious Disease; Molecular Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Xie, M. (2019). A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/8094

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xie, Mengyu. “A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy.” 2019. Thesis, University of South Florida. Accessed January 16, 2021. https://scholarcommons.usf.edu/etd/8094.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xie, Mengyu. “A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy.” 2019. Web. 16 Jan 2021.

Vancouver:

Xie M. A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy. [Internet] [Thesis]. University of South Florida; 2019. [cited 2021 Jan 16]. Available from: https://scholarcommons.usf.edu/etd/8094.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xie M. A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy. [Thesis]. University of South Florida; 2019. Available from: https://scholarcommons.usf.edu/etd/8094

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kentucky

22. El-Refai, Sherif M. EXPLORING THE EFFECT OF CHRONIC INFLAMMATION ON RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN CANCER.

Degree: 2018, University of Kentucky

URL: https://uknowledge.uky.edu/pharmacy_etds/82

► Precision medicine has allowed for the development of monoclonal antibodies that unmask the anti-tumor immune response. These agents have provided some patients durable clinical benefit.… (more)

Subjects/Keywords: Immune checkpoint inhibitors; biomarkers of response; health outcomes research; cancer; PD-1/PD-L1; Pharmacy and Pharmaceutical Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

El-Refai, S. M. (2018). EXPLORING THE EFFECT OF CHRONIC INFLAMMATION ON RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN CANCER. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/pharmacy_etds/82

Chicago Manual of Style (16^th Edition):

El-Refai, Sherif M. “EXPLORING THE EFFECT OF CHRONIC INFLAMMATION ON RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN CANCER.” 2018. Doctoral Dissertation, University of Kentucky. Accessed January 16, 2021. https://uknowledge.uky.edu/pharmacy_etds/82.

MLA Handbook (7^th Edition):

El-Refai, Sherif M. “EXPLORING THE EFFECT OF CHRONIC INFLAMMATION ON RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN CANCER.” 2018. Web. 16 Jan 2021.

Vancouver:

El-Refai SM. EXPLORING THE EFFECT OF CHRONIC INFLAMMATION ON RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN CANCER. [Internet] [Doctoral dissertation]. University of Kentucky; 2018. [cited 2021 Jan 16]. Available from: https://uknowledge.uky.edu/pharmacy_etds/82.

Council of Science Editors:

El-Refai SM. EXPLORING THE EFFECT OF CHRONIC INFLAMMATION ON RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN CANCER. [Doctoral Dissertation]. University of Kentucky; 2018. Available from: https://uknowledge.uky.edu/pharmacy_etds/82

Kyoto University

23. Mulati, Kumuluzi. VISTA expressed in tumor cells regulates T cell function .

Degree: 2019, Kyoto University

URL: http://hdl.handle.net/2433/242370

Subjects/Keywords: VISTA; immune checkpoint; cancer immunotherapy; B7-H5; PD-1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mulati, K. (2019). VISTA expressed in tumor cells regulates T cell function . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/242370

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mulati, Kumuluzi. “VISTA expressed in tumor cells regulates T cell function .” 2019. Thesis, Kyoto University. Accessed January 16, 2021. http://hdl.handle.net/2433/242370.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mulati, Kumuluzi. “VISTA expressed in tumor cells regulates T cell function .” 2019. Web. 16 Jan 2021.

Vancouver:

Mulati K. VISTA expressed in tumor cells regulates T cell function . [Internet] [Thesis]. Kyoto University; 2019. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2433/242370.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mulati K. VISTA expressed in tumor cells regulates T cell function . [Thesis]. Kyoto University; 2019. Available from: http://hdl.handle.net/2433/242370

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

24. Hartley, Genevieve. PD-L1 expression by tumor macrophages: regulation and signaling.

Degree: PhD, Cell and Molecular Biology, 2018, Colorado State University

URL: http://hdl.handle.net/10217/189353

To view the abstract, please see the full text of the document. Advisors/Committee Members: Dow, Steven (advisor), Schenkel, Alan (committee member), Gonzalez-Juarrero, Mercedes (committee member), Biller, Barbara (committee member).

Subjects/Keywords: canine; macrophage; cancer; tumor; immune checkpoint

…1 The first immune checkpoint: CTLA-4… …5 Future directions for immune checkpoint blockade… …110 ix CHAPTER 1 Review of the Literature The first immune checkpoint: CTLA-4. Tumor… …conditions, immune checkpoint molecules prevent autoimmunity and protect tissues from damage by… …CD152) was the first immune checkpoint molecule to be clinically targeted with monoclonal…

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APA (6^th Edition):

Hartley, G. (2018). PD-L1 expression by tumor macrophages: regulation and signaling. (Doctoral Dissertation). Colorado State University. Retrieved from http://hdl.handle.net/10217/189353

Chicago Manual of Style (16^th Edition):

Hartley, Genevieve. “PD-L1 expression by tumor macrophages: regulation and signaling.” 2018. Doctoral Dissertation, Colorado State University. Accessed January 16, 2021. http://hdl.handle.net/10217/189353.

MLA Handbook (7^th Edition):

Hartley, Genevieve. “PD-L1 expression by tumor macrophages: regulation and signaling.” 2018. Web. 16 Jan 2021.

Vancouver:

Hartley G. PD-L1 expression by tumor macrophages: regulation and signaling. [Internet] [Doctoral dissertation]. Colorado State University; 2018. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10217/189353.

Council of Science Editors:

Hartley G. PD-L1 expression by tumor macrophages: regulation and signaling. [Doctoral Dissertation]. Colorado State University; 2018. Available from: http://hdl.handle.net/10217/189353

University of Queensland

25. Addala, Venkateswara. Therapeutic Opportunity in Cancers with Poor Survival.

Degree: Faculty of Medicine, 2020, University of Queensland

URL: http://espace.library.uq.edu.au/view/UQ:9

► Next generation sequencing has allowed researchers to characterise the somatic landscape of cancer genomes, which has led to the discovery of biomarkers that may be… (more)

▼ Next generation sequencing has allowed researchers to characterise the somatic landscape of cancer genomes, which has led to the discovery of biomarkers that may be predictive and prognostic to targeted therapies. However, the efficacy of current targeted therapies has failed to raise the overall survival curve in many tumour types. Immunotherapy has shown a promising benefit in treating many tumours and demonstrated remarkable responses even at recurrent, relapse and metastasis stage. Tumour mutation burden (TMB) can stratify some responders and non-responders to Immunotherapies, but it is not perfect. Tumour whole genome sequencing (WGS) and RNA sequencing play a major role in deciphering tumour intrinsic-extrinsic factors and may improve prediction responses to immune checkpoint blockade therapies. This dissertation will explore computational tools that can be applied to understand complex tumour-immune milieu and that may predict a response to immunotherapy.Chapter 2 includes a comprehensive benchmarking analysis of bioinformatics tools to identify cancer-immunity interactions. In addition, tools to predict responses for immune checkpoint blockade therapies were evaluated on publicly available immunotherapy treated clinical datasets. Using this information an immunogenomics pipeline was developed with the bioinformatic tools that showed the best concordance with gold-standard in-vitro techniques. This pipeline was applied in subsequent chapters to predict immunotherapy responses and to identify various tumour immune escape mechanisms in tumour types that have a poor survival.In Chapter 3, I used the immunogenomics pipeline to analyse whole genome sequencing and RNA sequencing of malignant pleural mesothelioma (MPM). MPM is a rare, aggressive cancer associated with asbestos exposure and has very limited treatment options. Heterogeneity was observed in tumour intrinsic and extrinsic factors within MPM patient samples, including clonal selection of neoantigen presentation, altered gene expression profiles in neoantigen trafficking components and enriched immune cells within the tumour microenvironment. This profiling may help in to increase overall survival in mesothelioma by indicating patients who are more likely to be responsive to emerging immunotherapies and importantly providing mechanisms for why other patients may not respond.In chapter 4, I assessed various immune escape mechanisms of microsatellite stable (MSS) primary colorectal and matched liver metastasis tumours. MSS stable tumours are generally thought to be immunogenic “cold” tumours and remain as a major research challenge as they exist in an immune suppressed tumour microenvironment with low TMB. Through matched primary and metastasis WGS and RNAseq analysis I identified loss of heterozygosity of the HLA alleles, consistent neoantigen profiles, heterogeneity in T-cell repertoire expansion and diversity and other tumour microenvironment components that facilitate immune escape mechanisms in “cold” tumours. These findings highlight the mechanisms…

Subjects/Keywords: cancer immunotherapy; immune checkpoint blockade; neoantigens; whole genome sequencing; rna sequencing; mesothelioma; mss cold tumours; melanoma; tumour microenvironment; immune cells deconvolution; 0601 Biochemistry and Cell Biology; 0604 Genetics; 1107 Immunology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Addala, V. (2020). Therapeutic Opportunity in Cancers with Poor Survival. (Thesis). University of Queensland. Retrieved from http://espace.library.uq.edu.au/view/UQ:9

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Addala, Venkateswara. “Therapeutic Opportunity in Cancers with Poor Survival.” 2020. Thesis, University of Queensland. Accessed January 16, 2021. http://espace.library.uq.edu.au/view/UQ:9.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Addala, Venkateswara. “Therapeutic Opportunity in Cancers with Poor Survival.” 2020. Web. 16 Jan 2021.

Vancouver:

Addala V. Therapeutic Opportunity in Cancers with Poor Survival. [Internet] [Thesis]. University of Queensland; 2020. [cited 2021 Jan 16]. Available from: http://espace.library.uq.edu.au/view/UQ:9.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Addala V. Therapeutic Opportunity in Cancers with Poor Survival. [Thesis]. University of Queensland; 2020. Available from: http://espace.library.uq.edu.au/view/UQ:9

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center

26. Roh, Whijae. INTEGRATIVE CANCER IMMUNOGENOMIC ANALYSIS OF SERIAL MELANOMA BIOPSIES REVEALS CORRELATES OF RESPONSE AND RESISTANCE TO SEQUENTIAL CTLA-4 AND PD-1 BLOCKADE TREATMENT.

Degree: PhD, 2017, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/813

► Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and… (more)

▼ Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen–4 (CTLA-4) followed by programmed death receptor–1 (PD-1) by immunogenomic profile analyses from serial tumor biopsies. From immune profiling (12 marker immunohistochemistry and NanoString Gene Expression Profiling), we found that adaptive immune signatures in tumor biopsies obtained from early on-treatment time points are predictive of response to immune checkpoint blockade. We also demonstrated differential mechanistic signatures of tumor microenvironment induced by CTLA-4 and PD-1 blockade. Importantly, VEGFA was identified as a potential target of combination therapy withPD-1blockade. From genomic profiling (whole exome sequencing and T cell receptor sequencing), we demonstrated that a higher TCR clonality in pre-treatment biopsy was predictive of response to PD-1 but notCTLA-4blockade. We also observed increased TCR clonality after CTLA-4 blockade treatment in patients responding to the following PD-1 blockade treatment. Analysis of copy number alterations (CNAs) identified a higher burden of copy number loss in nonresponders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was nonredundant, suggesting the potential utility of these as a combinatorial biomarker to optimize patient care with checkpoint blockade therapy. In summary, our integrative cancer immunogenomic analysis shows that genomic and immune profiling of longitudinal tumor biopsies can identify novel biomarkers and resistance mechanisms of immune checkpoint blockade. Advisors/Committee Members: P. Andrew Futreal, Ph.D., James P. Allison, Ph.D., Giulio Draetta, M.D., Ph.D..

Subjects/Keywords: cancer immunology; immunotherapy; immune checkpoint blockade; CTLA-4; PD-1; genomics; melanoma; response; resistance; biomarker; Bioinformatics; Computational Biology; Genomics; Medical Immunology; Medicine and Health Sciences; Skin and Connective Tissue Diseases

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Roh, W. (2017). INTEGRATIVE CANCER IMMUNOGENOMIC ANALYSIS OF SERIAL MELANOMA BIOPSIES REVEALS CORRELATES OF RESPONSE AND RESISTANCE TO SEQUENTIAL CTLA-4 AND PD-1 BLOCKADE TREATMENT. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/813

Chicago Manual of Style (16^th Edition):

Roh, Whijae. “INTEGRATIVE CANCER IMMUNOGENOMIC ANALYSIS OF SERIAL MELANOMA BIOPSIES REVEALS CORRELATES OF RESPONSE AND RESISTANCE TO SEQUENTIAL CTLA-4 AND PD-1 BLOCKADE TREATMENT.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed January 16, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/813.

MLA Handbook (7^th Edition):

Roh, Whijae. “INTEGRATIVE CANCER IMMUNOGENOMIC ANALYSIS OF SERIAL MELANOMA BIOPSIES REVEALS CORRELATES OF RESPONSE AND RESISTANCE TO SEQUENTIAL CTLA-4 AND PD-1 BLOCKADE TREATMENT.” 2017. Web. 16 Jan 2021.

Vancouver:

Roh W. INTEGRATIVE CANCER IMMUNOGENOMIC ANALYSIS OF SERIAL MELANOMA BIOPSIES REVEALS CORRELATES OF RESPONSE AND RESISTANCE TO SEQUENTIAL CTLA-4 AND PD-1 BLOCKADE TREATMENT. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Jan 16]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/813.

Council of Science Editors:

Roh W. INTEGRATIVE CANCER IMMUNOGENOMIC ANALYSIS OF SERIAL MELANOMA BIOPSIES REVEALS CORRELATES OF RESPONSE AND RESISTANCE TO SEQUENTIAL CTLA-4 AND PD-1 BLOCKADE TREATMENT. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/813

University of Hawaii

27. Clements, Danielle M. REGULATION OF CD8 T-CELL FUNCTION BY MULTIPLE NEGATIVE IMMUNE CHECKPOINT MOLECULES DURING HTLV-1 INFECTION.

Degree: 2020, University of Hawaii

URL: http://hdl.handle.net/10125/68913

Subjects/Keywords: Translation studies; Immunology; HTLV-1; Immune checkpoint blockade; Immunotherapy; T-cell dysfunction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Clements, D. M. (2020). REGULATION OF CD8 T-CELL FUNCTION BY MULTIPLE NEGATIVE IMMUNE CHECKPOINT MOLECULES DURING HTLV-1 INFECTION. (Thesis). University of Hawaii. Retrieved from http://hdl.handle.net/10125/68913

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Clements, Danielle M. “REGULATION OF CD8 T-CELL FUNCTION BY MULTIPLE NEGATIVE IMMUNE CHECKPOINT MOLECULES DURING HTLV-1 INFECTION.” 2020. Thesis, University of Hawaii. Accessed January 16, 2021. http://hdl.handle.net/10125/68913.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Clements, Danielle M. “REGULATION OF CD8 T-CELL FUNCTION BY MULTIPLE NEGATIVE IMMUNE CHECKPOINT MOLECULES DURING HTLV-1 INFECTION.” 2020. Web. 16 Jan 2021.

Vancouver:

Clements DM. REGULATION OF CD8 T-CELL FUNCTION BY MULTIPLE NEGATIVE IMMUNE CHECKPOINT MOLECULES DURING HTLV-1 INFECTION. [Internet] [Thesis]. University of Hawaii; 2020. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10125/68913.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Clements DM. REGULATION OF CD8 T-CELL FUNCTION BY MULTIPLE NEGATIVE IMMUNE CHECKPOINT MOLECULES DURING HTLV-1 INFECTION. [Thesis]. University of Hawaii; 2020. Available from: http://hdl.handle.net/10125/68913

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

George Mason University

28. Dey, Douglass. Investigation of Small Peptide Inhibitors on PD-1 PD-L1 Protein-Protein Interactions .

Degree: George Mason University

URL: http://hdl.handle.net/1920/11121

► Cancer is a complex disease in which abnormal cells divide uncontrollably and invade body tissues, leading to eventual organ failure and death. These abnormal cells… (more)

▼ Cancer is a complex disease in which abnormal cells divide uncontrollably and invade body tissues, leading to eventual organ failure and death. These abnormal cells are able to grow and spread by evading recognition and destruction by the immune system through multiple mechanisms. Utilization of immune checkpoints, which are regulators of the immune system that prevent autoimmunity, is one such mechanism exploited by cancer cells. A specific immune checkpoint pathway involves tumor cells upregulating PD-L1 or programmed death ligand 1. When bound to its receptor PD-1, or programmed death protein 1, PD-L1 prevents the anti-tumor immune response normally responsible for clearing abnormal cells throughout the body. Within the past decade, a new class of drugs called immune checkpoint inhibitors have been developed to block this interaction and unleash the patient’s immune system on their tumor cells. While these drugs have seen promising results for some patients, there are still limitations that need to be overcome. Many of the existing cancer immunotherapies are in monoclonal antibody form and have problems with specificity, tissue penetration, route of administration, and are expensive to produce. In this study, we characterized and tested eight different small peptide inhibitors to the PD-1 PD-L1 pathway that were developed using protein painting, a novel technique used to identify specific hotspots within the binding interface. These small peptide inhibitors have the potential to be more specific than antibody therapies by exclusively targeting the protein-protein interface and could potentially be optimized to allow for oral administration. We also characterized various molecular dyes for future protein painting and introduced preliminary studies which optimize cell painting, a novel technique that uses molecular dyes on the surface of living cells to elucidate new drug targets and create whole cell “interactomes” between immune and target cell types. Advisors/Committee Members: Luchini, Alessandra (advisor).

Subjects/Keywords: PD-1; PD-L1; small peptide inhibitors; checkpoint inhibition; immune checkpoints; cancer immunotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dey, D. (n.d.). Investigation of Small Peptide Inhibitors on PD-1 PD-L1 Protein-Protein Interactions . (Thesis). George Mason University. Retrieved from http://hdl.handle.net/1920/11121

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dey, Douglass. “Investigation of Small Peptide Inhibitors on PD-1 PD-L1 Protein-Protein Interactions .” Thesis, George Mason University. Accessed January 16, 2021. http://hdl.handle.net/1920/11121.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dey, Douglass. “Investigation of Small Peptide Inhibitors on PD-1 PD-L1 Protein-Protein Interactions .” Web. 16 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Dey D. Investigation of Small Peptide Inhibitors on PD-1 PD-L1 Protein-Protein Interactions . [Internet] [Thesis]. George Mason University; [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1920/11121.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Dey D. Investigation of Small Peptide Inhibitors on PD-1 PD-L1 Protein-Protein Interactions . [Thesis]. George Mason University; Available from: http://hdl.handle.net/1920/11121

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Arizona State University

29. Nikolopoulou, Elpiniki. Mathematical Modeling of Novel Cancer Immunotherapies.

Degree: Applied Mathematics, 2020, Arizona State University

URL: http://repository.asu.edu/items/62684

Subjects/Keywords: Applied mathematics; Avelumab; Identifiability; Immune checkpoint Inhibitors; Immunotherapy; Mathematical Modeling; Oncolytic Virus Therapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nikolopoulou, E. (2020). Mathematical Modeling of Novel Cancer Immunotherapies. (Doctoral Dissertation). Arizona State University. Retrieved from http://repository.asu.edu/items/62684

Chicago Manual of Style (16^th Edition):

Nikolopoulou, Elpiniki. “Mathematical Modeling of Novel Cancer Immunotherapies.” 2020. Doctoral Dissertation, Arizona State University. Accessed January 16, 2021. http://repository.asu.edu/items/62684.

MLA Handbook (7^th Edition):

Nikolopoulou, Elpiniki. “Mathematical Modeling of Novel Cancer Immunotherapies.” 2020. Web. 16 Jan 2021.

Vancouver:

Nikolopoulou E. Mathematical Modeling of Novel Cancer Immunotherapies. [Internet] [Doctoral dissertation]. Arizona State University; 2020. [cited 2021 Jan 16]. Available from: http://repository.asu.edu/items/62684.

Council of Science Editors:

Nikolopoulou E. Mathematical Modeling of Novel Cancer Immunotherapies. [Doctoral Dissertation]. Arizona State University; 2020. Available from: http://repository.asu.edu/items/62684

30. Wierz, Marina. Characterization of the Tumor Microenvironment in Chronic Lymphocytic Leukemia by Mass Cytometry : Implications for Immunotherapy : Caractérisation du microenvironnement tumoral dans la leucémie lymphoïde chronique par cytométrie de masse : implications pour l'immunothérapie.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2020, université Paris-Saclay

URL: http://www.theses.fr/2020UPASL020

►

La leucémie lymphoïde chronique (LLC), la leucémie la plus fréquente chez l'adulte, est caractérisée par l'accumulation de lymphocytes B matures dans le sang périphérique et… (more)

▼

La leucémie lymphoïde chronique (LLC), la leucémie la plus fréquente chez l'adulte, est caractérisée par l'accumulation de lymphocytes B matures dans le sang périphérique et les tissus lymphoïdes. La progression de la LLC est fortement dépendante des interactions complexes au sein du microenvironnement tumoral (TME) et malgré les récentes avancées dans le traitement de la LLC ciblant la TME, la LLC reste une maladie incurable. Par conséquent, nous voulions caractériser en profondeur le paysage immunitaire dans le TME dans la LLC murine et humaine afin d'identifier de nouvelles cibles potentielles pour une approche immunothérapeutique. À cette fin, nous avons effectué une caractérisation complète et approfondie par cytométrie de masse à haute dimension pour établir une cartographie approfondie des sous-populations de cellules immunitaires. Nous démontrons que les changements pertinents dans la composition des cellules immunitaires, en particulier l'expansion de sous-populations spécifiques de cellules immunitaires lymphoïdes et myéloïdes, sont associés à une forte suppression immunitaire contribuant ainsi à un phénotype d'échappement dans la LLC. Ces changements associés à la LLC peuvent être restaurés dans les modèles précliniques par un double blocage du point de contrôle immunitaire PD1/LAG3. De plus, nous démontrons une forte hétérogénéité des cellules T entre les patients qui peut être stratifiée en fonction de leur profil de cellules T, et la corrélation de sous-ensembles de cellules T spécifiques avec le temps jusqu'au traitement initial, mettant en évidence leur valeur pronostique potentielle. En conclusion, avec cette première étude CyTOF dans la LLC, nous avons élargi les connaissances actuelles sur la complexité phénotypique du TME. Nous avons démontré que le double ciblage des points de contrôle immunitaires contrôlait efficacement le développement de la LLC dans les modèles précliniques et pouvait donc avoir des avantages potentiels dans la LLC pour restaurer une immunité anti-tumorale fonctionnelle.

Chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults, is characterized by the accumulation of mature B lymphocytes in peripheral blood and lymphoid tissues. The progression of CLL is highly dependent on complex interactions within the tumor microenvironment (TME) and despite recent advances in CLL treatment targeting the TME, CLL remains an incurable disease. Therefore, we wanted to deeply characterize the immune landscape in the TME in murine and human CLL to identify novel potential targets for an immunotherapeutic approach. For this purpose, we performed a comprehensive and extensive characterization by high-dimensional mass cytometry to establish an extensive cartography of immune cell subsets. We demonstrated that relevant changes in the immune cell composition, especially the expansion of specific lymphoid and myeloid immune cell subsets, are associated with strong immune suppression thereby contributing to an escape phenotype in CLL. These CLL-associated changes can be restored…

Advisors/Committee Members: Janji, Bassam (thesis director), Moussay, Etienne (thesis director).

Subjects/Keywords: Leucémie lymphoïde chronique; Microenvironment tumoral; Cytométrie de masse; Imunothérapie; Point de contrôle immunitaire; Chronic lymphocytic leukemia; Tumor microenvironment; Mass cytometry; Immunotherapy; Immune checkpoint

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wierz, M. (2020). Characterization of the Tumor Microenvironment in Chronic Lymphocytic Leukemia by Mass Cytometry : Implications for Immunotherapy : Caractérisation du microenvironnement tumoral dans la leucémie lymphoïde chronique par cytométrie de masse : implications pour l'immunothérapie. (Doctoral Dissertation). université Paris-Saclay. Retrieved from http://www.theses.fr/2020UPASL020

Chicago Manual of Style (16^th Edition):

Wierz, Marina. “Characterization of the Tumor Microenvironment in Chronic Lymphocytic Leukemia by Mass Cytometry : Implications for Immunotherapy : Caractérisation du microenvironnement tumoral dans la leucémie lymphoïde chronique par cytométrie de masse : implications pour l'immunothérapie.” 2020. Doctoral Dissertation, université Paris-Saclay. Accessed January 16, 2021. http://www.theses.fr/2020UPASL020.

MLA Handbook (7^th Edition):

Wierz, Marina. “Characterization of the Tumor Microenvironment in Chronic Lymphocytic Leukemia by Mass Cytometry : Implications for Immunotherapy : Caractérisation du microenvironnement tumoral dans la leucémie lymphoïde chronique par cytométrie de masse : implications pour l'immunothérapie.” 2020. Web. 16 Jan 2021.

Vancouver:

Wierz M. Characterization of the Tumor Microenvironment in Chronic Lymphocytic Leukemia by Mass Cytometry : Implications for Immunotherapy : Caractérisation du microenvironnement tumoral dans la leucémie lymphoïde chronique par cytométrie de masse : implications pour l'immunothérapie. [Internet] [Doctoral dissertation]. université Paris-Saclay; 2020. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2020UPASL020.

Council of Science Editors:

Wierz M. Characterization of the Tumor Microenvironment in Chronic Lymphocytic Leukemia by Mass Cytometry : Implications for Immunotherapy : Caractérisation du microenvironnement tumoral dans la leucémie lymphoïde chronique par cytométrie de masse : implications pour l'immunothérapie. [Doctoral Dissertation]. université Paris-Saclay; 2020. Available from: http://www.theses.fr/2020UPASL020

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Open Access Theses and Dissertations