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PD-1 PD-L1

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https://www.readbyqxmd.com/read/28109400/tumor-infiltrating-lymphocytes-in-gastrointestinal-tumors-controversies-and-future-clinical-implications
#1
REVIEW
Cinzia Solinas, Grazia Pusole, Laura Demurtas, Marco Puzzoni, Roberta Mascia, Gilberto Morgan, Riccardo Giampieri, Mario Scartozzi
Chronic inflammation following infections, autoimmune diseases or exposure to environmental irritants plays a crucial role in tumor development and influences the host immune response to neoplastic cells. The presence of an anti-tumor immune infiltrate is often associated with better outcomes in gastro-intestinal primary cancers, particularly in those with high microsatellite instability (MSI-H). Immunotherapeutic drugs inhibiting the PD-1 and PD-L1 pathway showed promising results in the treatment of these patients in the metastatic setting...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28107610/tonsil-derived-mesenchymal-stem-cells-t-mscs-prevent-th17-mediated-autoimmune-response-via-regulation-of-the-programmed-death-1-programmed-death-ligand-1-pd-1-pd-l1-pathway
#2
Ji-Yon Kim, Minhwa Park, Yu-Hee Kim, Kyung-Ha Ryu, Kyung Ho Lee, Kyung-Ah Cho, So-Youn Woo
Our knowledge of the immunomodulatory role of mesenchymal stem cells (MSCs) in both the innate and adaptive immune systems has dramatically expanded, providing great promise for treating various autoimmune diseases. However, the contribution of MSCs to Th17 dominant immune disease, such as psoriasis and its underlying mechanism remains elusive. In this study, we demonstrated that human palatine tonsil-derived MSCs (T-MSCs) constitutively express both the membrane-bound and soluble forms of programmed death-ligand 1 (PD-L1), which enables T-MSCs to be distinguished from MSCs originating from other organs (i...
January 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#3
Yanheng Wu, Mingshui Chen, Peihong Wu, Chen Chen, Zhi Ping Xu, Wenyi Gu
Here we report the expression of programmed cell death ligand 1/2 (PD-L1/L2) in breast and colon cancer stem cells (CSCs). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated that PD-L1 expression was higher in CSCs of both cancers compared to non-stem like cancer cells. Consistent with this, detection of cellular PD-L1 proteins by Western blot assay also showed increased PD-L1 protein in CSCs. In contrast, only trance amounts of PD-L2 were detected in CSCs of both cancers...
January 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28107186/the-combination-of-pd-l1-expression-and-decreased-tumor-infiltrating-lymphocytes-is-associated-with-a-poor-prognosis-in-triple-negative-breast-cancer
#4
Hitomi Mori, Makoto Kubo, Rin Yamaguchi, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Yasuhiro Okumura, Masayuki Okido, Mai Yamada, Masaya Kai, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura
This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28104537/correlation-between-classic-driver-oncogene-mutations-in-egfr-alk-or-ros1-and-22c3-pd-l1-%C3%A2-50-expression-in-lung-adenocarcinoma
#5
Deepa Rangachari, Paul A VanderLaan, Meghan Shea, Xiuning Le, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Targeted somatic genomic analysis (EGFR, ALK and ROS1) and PD-L1 tumor proportion score (TPS) by immunohistochemistry (IHC) are used for selection of 1(st)-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. METHODS: We retrospectively probed the first 71 lung adenocarcinoma-patient pairs from our institution analyzed for PD-L1 IHC using the clone 22C3 pharmDx kit and evaluated co-occurrence of genomic aberrations along with clinical-pathologic characteristics...
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28102259/elements-of-cancer-immunity-and-the-cancer-immune-set-point
#6
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
#7
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/28096717/immune-checkpoint-inhibitors-in-the-era-of-precision-medicine-what-radiologists-should-know
#8
REVIEW
Marta Braschi-Amirfarzan, Sree Harsha Tirumani, Frank Stephen Hodi, Mizuki Nishino
Over the past five years immune-checkpoint inhibitors have dramatically changed the therapeutic landscape of advanced solid and hematologic malignancies. The currently approved immune-checkpoint inhibitors include antibodies to cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1 and PD-L2). Response to immune-checkpoint inhibitors is evaluated on imaging using the immune-related response criteria. Activation of immune system results in a unique toxicity profile termed immune-related adverse events...
January 2017: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/28096683/clinicopathological-and-immunohistochemical-features-of-lung-invasive-mucinous-adenocarcinoma-based-on-computed-tomography-findings
#9
Katsuhiko Shimizu, Riki Okita, Shinsuke Saisho, Ai Maeda, Yuji Nojima, Masao Nakata
BACKGROUND: We performed an analysis to clarify differences in clinicopathological and molecular features of lung invasive mucinous adenocarcinoma (IMA) based on computed tomography (CT) findings and their impact on prognosis. PATIENTS AND METHODS: On the basis of CT findings, we divided lung IMA into three subtypes: solid, bubbling, and pneumonic. We then investigated differences in clinicopathological characteristics, prognosis, and the expressions of well-identified biomarkers, including cyclooxygenase-2 (Cox-2), excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M1 (RRM1), class III beta-tubulin, thymidylate synthase (TS), secreted protein acidic and rich in cysteine (SPARC), programmed cell death-1 ligand-1 (PD-L1), and epidermal growth factor receptor mutation, among the three subtypes...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28096390/modification-of-host-dendritic-cells-by-microchimerism-derived-extracellular-vesicles-generates-split-tolerance
#10
William Bracamonte-Baran, Jonathan Florentin, Ying Zhou, Ewa Jankowska-Gan, W John Haynes, Weixiong Zhong, Todd V Brennan, Partha Dutta, Frans H J Claas, Jon J van Rood, William J Burlingham
Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in some, MMc magnitude was enough to cause membrane alloantigen acquisition (mAAQ; "cross-dressing") of host dendritic cells (DCs). Extracellular vesicle (EV)-enriched serum fractions from mAAQ(+), but not from non-mAAQ, mice reproduced the DC cross-dressing phenomenon in vitro...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096371/cox2-mpges1-pge2-pathway-regulates-pd-l1-expression-in-tumor-associated-macrophages-and-myeloid-derived-suppressor-cells
#11
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
#12
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/28086852/pd-l1-expression-in-papillary-renal-cell-carcinoma
#13
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
#14
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
#15
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
#16
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
#17
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/28074937/circulating-t-lymphocyte-subsets-cytokines-and-immune-checkpoint-inhibitors-in-patients-with-bipolar-ii-or-major-depression-a-preliminary-study
#18
Wei Wu, Ya-Li Zheng, Li-Ping Tian, Jian-Bo Lai, Chan-Chan Hu, Peng Zhang, Jing-Kai Chen, Jian-Bo Hu, Man-Li Huang, Ning Wei, Wei-Juan Xu, Wei-Hua Zhou, Shao-Jia Lu, Jing Lu, Hong-Li Qi, Dan-Dan Wang, Xiao-Yi Zhou, Jin-Feng Duan, Yi Xu, Shao-Hua Hu
This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#19
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
#20
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
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