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pd-l1 and cancer

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https://www.readbyqxmd.com/read/28102259/elements-of-cancer-immunity-and-the-cancer-immune-set-point
#1
Daniel S Chen, Ira Mellman
Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28101034/a-case-of-poorly-differentiated-large-cell-neuroendocrine-carcinoma-of-the-cecum-a-rare-malignancy-with-review-of-the-literature
#2
Andrew T Mertz, Michelle A Ojemuyiwa
Poorly differentiated neuroendocrine carcinomas (NECs) are rare tumors that can arise anywhere along the gastrointestinal tract. They often present in advanced stage and portend a poor prognosis when compared to adenocarcinomas of the same stage. Characterization of these tumors is best accomplished with tissue biopsy, as peripheral tumor markers commonly used in NECs are of little utility. Therapeutic strategies often involve chemotherapeutic regimens that have been used to treat small-cell lung cancer. Recent studies have shown that programmed death-ligand 1 (PD-L1) expression within poorly differentiated NECs is a poor prognostic indicator...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28096505/the-neuropilin-2-isoform-nrp2b-uniquely-supports-tgf%C3%AE-mediated-progression-in-lung-cancer
#3
Robert M Gemmill, Patrick Nasarre, Joyce Nair-Menon, Federico Cappuzzo, Lorenza Landi, Armida D'Incecco, Hidetaka Uramoto, Takeshi Yoshida, Eric B Haura, Kent Armeson, Harry A Drabkin
Neuropilins (NRP1 and NRP2) are co-receptors for heparin-binding growth factors and class 3 semaphorins. Different isoforms of NRP1 and NRP2 are produced by alternative splicing. We found that in non-small cell lung cancer (NSCLC) cell lines, transforming growth factor-β (TGFβ) signaling preferentially increased the abundance of NRP2b. NRP2b and NRP2a differ only in their carboxyl-terminal regions. Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096371/cox2-mpges1-pge2-pathway-regulates-pd-l1-expression-in-tumor-associated-macrophages-and-myeloid-derived-suppressor-cells
#4
Victor Prima, Lyudmila N Kaliberova, Sergey Kaliberov, David T Curiel, Sergei Kusmartsev
In recent years, it has been established that programmed cell death protein ligand 1 (PD-L1)-mediated inhibition of activated PD-1(+) T lymphocytes plays a major role in tumor escape from immune system during cancer progression. Lately, the anti-PD-L1 and -PD-1 immune therapies have become an important tool for treatment of advanced human cancers, including bladder cancer. However, the underlying mechanisms of PD-L1 expression in cancer are not fully understood. We found that coculture of murine bone marrow cells with bladder tumor cells promoted strong expression of PD-L1 in bone marrow-derived myeloid cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093480/comprehensive-screening-for-pd-l1-expression-in-thyroid-cancer
#5
Soomin Ahn, Tae Hyuk Kim, Sun Wook Kim, Chang Seok Ki, Hye Won Jang, Jee Soo Kim, Jung Han Kim, Jun-Ho Choe, Jung Hee Shin, Soo Yeon Hahn, Young Lyun Oh, Jae Hoon Chung
PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142)...
February 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28090751/a-safety-checkpoint-to-eliminate-cancer-risk-of-the-immune-evasive-cells-derived-from-human-embryonic-stem-cells
#6
Jingjin He, Zhili Rong, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the co-expression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28086852/pd-l1-expression-in-papillary-renal-cell-carcinoma
#7
Takanobu Motoshima, Yoshihiro Komohara, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda, Masatoshi Eto
BACKGROUND: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2). METHODS: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC). RESULT: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen...
January 13, 2017: BMC Urology
https://www.readbyqxmd.com/read/28079291/prognostic-value-of-pd-l1-in-breast-cancer-a-meta-analysis
#8
Changjun Wang, Hanjiang Zhu, Yidong Zhou, Feng Mao, Yan Lin, Bo Pan, Xiaohui Zhang, Qianqian Xu, Xin Huang, Qiang Sun
Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies...
January 12, 2017: Breast Journal
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#9
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28076847/programmed-cell-death-ligand-1-expression-predicts-survival-in-patients-with-gastric-carcinoma-with-microsatellite-instability
#10
Junhun Cho, Jeeyun Lee, Heejin Bang, Seung Tae Kim, Se Hoon Park, Ji Yeong An, Min Gew Choi, Joon Ho Lee, Tae Sung Sohn, Jae Moon Bae, Won Ki Kang, Sung Kim, Kyoung-Mee Kim
Programmed death-ligand 1 (PD-L1) is expressed in a subgroup of gastric cancers that may benefit from immunotherapy. Microsatellite instability-high (MSI-H) is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1. The relationship between PD-L1 expression and MSI-H status remains poorly understood. In this study, we investigated PD-L1 expression in patients with MSI-H gastric cancer. We analyzed PD-L1 expression in 78 MSI-H gastric cancer tissue samples using immunohistochemistry...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075442/increased-expression-of-pd%C3%A2-l1-by-the-human-papillomavirus-16-e7-oncoprotein-inhibits-anticancer-immunity
#11
Chaoqi Liu, Jiao Lu, Huiqun Tian, Wei Du, Lin Zhao, Jing Feng, Ding Yuan, Zhiying Li
Cytotoxic T lymphocyte dysfunction is frequently associated with PD‑L1/PD‑1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)‑induced evasion of cervical cancer cells to the host immune system via the programmed death ligand  1/programmed death 1 (PD‑L1/PD‑1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD‑L1 in cervical tissues was observed when compared with normal cervical tissues...
January 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#12
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28073845/agreement-between-programmed-cell-death-ligand-1-diagnostic-assays-across-multiple-protein-expression-cut-offs-in-non-small-cell-lung-cancer
#13
Marianne J Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Marietta Scott, Paul Scorer, Hytham Al-Masri, Marlon Rebelatto, Jill Walker
PURPOSE: agents:Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized and different assay methods could lead to inappropriate treatment selection...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28073774/temporally-distinct-pd-l1-expression-by-tumor-and-host-cells-contributes-to-immune-escape
#14
Takuro Noguchi, Jeffrey P Ward, Matthew M Gubin, Cora D Arthur, Sang Hun Lee, Jasreet Hundal, Mark J Selby, Robert F Graziano, Elaine R Mardis, Alan J Korman, Robert D Schreiber
Antibody blockade of programmed death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28072971/-expression-of-pd-1-pd-l1-in-triple-negative-breast-carcinoma-and-its-significance
#15
W Zhang, G X Xu, J J Li, X Liu, Y J Chen, F Zhang
Objective: To investigate the correlation between the expression of PD-1, PD-L1 and clinicopathologic parameters in triple negative breast carcinoma (TNBC). Methods: Samples from 151 patients with TNBC and 65 cases of other breast carcinomas (non-TNBC) were examined for PD-L1 and PD-1 expression by immunohistochemical staining on tissue microarray. Results: The expression of PD-L1 and PD-1 in the tumor cells and interstitial lymphocytes in TNBC was significantly (P<0.05)higher than that in non-TNBC.In TNBC, the expression rates of PD-L1 in the cancer nests and stroma were 16...
January 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28072716/pneumonitis-in-cancer-patients-receiving-anti-pd-1-and-radiotherapies-three-case-reports
#16
Chieh-Sheng Lu, Jin-Hwang Liu
INTRODUCTION: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28069723/a-novel-murine-gitr-ligand-fusion-protein-induces-antitumor-activity-as-a-monotherapy-which-is-further-enhanced-in-combination-with-an-ox40-agonist
#17
Rebecca Leyland, Amanda Watkins, Kathy Mulgrew, Nicholas Holoweckyj, Lisa Bamber, Natalie J Tigue, Emily Offer, John Andrews, Li Yan, Stefanie Mullins, Michael D Oberst, Jane Coates Ulrichsen, David A Leinster, Kelly A McGlinchey, Lesley Young, Michelle Morrow, Scott A Hammond, Philip R Mallinder, Athula Herath, Ching Ching Leow, Robert W Wilkinson, Ross Stewart
PURPOSE: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy. EXPERIMENTAL DESIGN: The EC50 value of the mGITRL-FP was compared to an anti-GITR antibody in an in vitro agonistic cell based reporter assay. We assessed the impact of dose, schedule and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared to an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models...
January 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28066581/pd-l1-expression-in-lung-cancer
#18
EDITORIAL
Chad Tang, Joe Y Chang
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28063623/immune-checkpoint-inhibitors-in-lung-cancer-an-unheralded-opportunity
#19
R Marshall, A Popple, T Kordbacheh, J Honeychurch, C Faivre-Finn, T Illidge
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. Over 70% of patients present with locally advanced, non-resectable or metastatic disease and despite improvements in chemoradiotherapy regimens and the development of molecularly targeted agents, 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern. Currently there remains an unmet need in effectively treating and inducing durable responses in advanced disease...
January 4, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28061450/th1high-in-tumor-microenvironment-is-an-indicator-of-poor-prognosis-for-patients-with-nsclc
#20
Huang Jian, Shen Fangrong, Huang Haitao, Ling Chunhua, Zhang Guangbo
CD4+Th subsets play an important role in tumor progression but their expression characteristics and clinical significance in human tumor microenvironment remains unclear. In this study, we aim to analyze the expression and clinical significance of tissue-infiltrating Th1, Th2 and Th17 in lung cancer by flow cytometry. We found that the frequency of CD3+CD4+IFN-γ+Th1 in tumor nest was significantly lower than that in tumor boundary, adjacent normal lung tissue or corresponding lymph node tissue; the frequency of CD3+CD4+IL-4+Th2 in tumor nest was significantly higher than that in tumor boundary, adjacent normal lung tissue or corresponding lymph node tissue; the frequency of CD3+CD4+IL-17+Th17 in tumor nest was significantly lower than that in tumor boundary, but not adjacent normal tissue or corresponding lymph node tissue...
January 3, 2017: Oncotarget
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