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Program death ligand 1/2

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https://www.readbyqxmd.com/read/29225166/apatinib-inhibits-migration-and-invasion-as-well-as-pd-l1-expression-in-osteosarcoma-by-targeting-stat3
#1
Bingxin Zheng, Tingting Ren, Yi Huang, Wei Guo
The cure rate of osteosarcoma has not improved in the past 30 years. The new treatments and drugs is urgently needed, especially for metastatic osteosarcoma. Anti-angiogenesis therapy and immunotherapy has got promising anti-tumor effects in various tumors. It is hypothesised that combining checkpoint inhibitor immunotherapies with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. However, its underlying mechanism remain largely uninvestigated. To investigate the clinical significance of vascular endothelial growth factor receptor-2 (VEGFR2) and programmed death ligand-1 (PD-L1) in osteosarcoma, we analyzes their expression levels in 93 osteosarcoma specimens by immunohistochemistry...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29217288/avelumab-in-metastatic-urothelial-carcinoma-after-platinum-failure-javelin-solid-tumor-pooled-results-from-two-expansion-cohorts-of-an-open-label-phase-1-trial
#2
Manish R Patel, John Ellerton, Jeffrey R Infante, Manish Agrawal, Michael Gordon, Raid Aljumaily, Carolyn D Britten, Luc Dirix, Keun-Wook Lee, Mathew Taylor, Patrick Schöffski, Ding Wang, Alain Ravaud, Arnold B Gelb, Junyuan Xiong, Galit Rosen, James L Gulley, Andrea B Apolo
BACKGROUND: The approval of anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 agents has expanded treatment options for patients with locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal anti-PD-L1 antibody, has shown promising antitumour activity and safety in this disease. We aimed to assess the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab and to assess antitumour activity of this drug in post-platinum patients...
December 4, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29209527/pembrolizumab-as-second-line-therapy-in-non-small-cell-lung-cancer-in-northern-norway-budget-impact-and-expected-gain-a-model-based-analysis
#3
Jan Norum, Margareth Aarag Antonsen, Terje Tollåli, Khalid Al-Shibli, Gry Andersen, Kristin Helene Svanqvist, Nina Helbekkmo
Background: Pembrolizumab is a new drug approved in several countries for second-line therapy in non-small cell lung cancer (NSCLC) being programmed cell death ligand (PD-L1) positive. This drug has a high cost, and the cost-effectiveness ratio has been debated. Patients and methods: The budget impact to the Northern Norwegian Regional Health Authority trust of implementing pembrolizumab in second-line therapy in patients with PD-L1-positive NSCLC was calculated...
2017: ESMO Open
https://www.readbyqxmd.com/read/29208565/mismatch-repair-deficient-colorectal-cancer-a-model-of-immunogenic-and-immune-cell-rich-tumor-despite-nonsignificant-pd-l1-expression-in-tumor-cells
#4
Glen Le Flahec, Bogdan Badic, Briac Guibourg, Laurent Doucet, Jean-Pierre Bail, Pascale Marcorelles, Ulrike Schick, Arnaud Uguen
Mismatch repair-deficient colorectal cancers (CRC) are good responders to anti-programmed cell death ligand-1 (PD-L1) immunotherapy, but the value of PD-L1 testing remains unclear. We studied PD-L1 expression and the tumor immune microenvironment in mismatch repair-deficient (dMMR) CRC as a model of good responders to immunotherapy. We examined 35 dMMR and 34 mismatch repair-proficient (pMMR) CRC using immune cell markers (CD3, CD4, CD8, CD20, CD68, and FOXP3) as well as PD-1 and PD-L1 immunohistochemistry staining in whole tumor specimens and tissue microarray slides to compare 4r PD-L1 immunohistochemistry clones (SP142, E1L3N, 22C3, and 28...
December 2, 2017: Human Pathology
https://www.readbyqxmd.com/read/29206673/pd-l1-expression-tumor-infiltrating-lymphocytes-and-clinical-outcome-in-patients-with-surgically-resected-esophageal-cancer
#5
Taisuke Yagi, Yoshifumi Baba, Takatsugu Ishimoto, Masaaki Iwatsuki, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Hideo Baba
OBJECTIVES: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. SUMMARY BACKGROUND DATA: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. METHODS: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis...
December 4, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/29195116/pd-l1-status-does-not-predict-the-outcome-of-braf-inhibitor-therapy-in-metastatic-melanoma
#6
Katrin Schaper-Gerhardt, Steven Okoye, Rudolf Herbst, Jens Ulrich, Patrick Terheyden, Claudia Pföhler, Jochen S Utikal, Alexander Kreuter, Peter Mohr, Edgar Dippel, Imke Satzger, Antje Sucker, Dirk Schadendorf, Selma Ugurel, Ralf Gutzmer
BACKGROUND: Targeted therapies with BRAF plus MEK inhibitors (BRAFi; MEKi) represent the major treatment strategy for patients with BRAF-mutated metastatic melanoma (MM). Previous analyses suggested a correlation between programmed death-ligand 1 (PD-L1) expression in tumour tissues and the outcome of targeted therapies. This study investigated PD-L1 as a potential predictive biomarker of BRAFi-based targeted therapies in MM patients. PATIENTS AND METHODS: We analysed two independent cohorts of BRAF V600-mutated MM patients undergoing BRAFi-based therapies for PD-L1 expression in pre-treatment tumour tissues...
November 28, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29189265/development-of-a-diagnostic-programmed-cell-death-1-ligand-1-immunohistochemistry-assay-for-nivolumab-therapy-in-melanoma
#7
Therese Phillips, Molly M Millett, Xiaoling Zhang, Malinka Jansson, Rachel Cleveland, Pauline Simmons, Gregory Cherryholmes, Josette Carnahan, Josette William, Betsy Spaulding, Ilana R Satnick, H David Inzunza, Clive Taylor, John Cogswell, James Novotny, Emin Oroudjev, Henrik Winther
Nivolumab is a monoclonal antibody that blocks the interaction between programmed cell death 1 (PD1) and programmed cell death 1-ligand 1 (PD-L1), resulting in enhanced antitumor activity by the immune system. Nivolumab is currently approved by the US Food and Drug Administration (FDA) for melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, and urothelial carcinoma. PD-L1 IHC 28-8 pharmDx is FDA-approved as a complementary diagnostic for immunohistochemical (IHC) detection of PD-L1 in non-squamous NSCLC and melanoma...
October 20, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29187883/programmed-cell-death-ligand-1-protein-levels-predicted-survival-of-non-small-cell-lung-cancer
#8
Shaohua Cui, Xinying Su, Lili Dong, Jialin Qian, Lin Ye, Tianwei Zhang, Haihua Fu, Hulin Han, Jiaqi Huang, Yihong Yao, Yi Gu, Liyan Jiang
Objective: To investigate the relationship between programmed death ligand 1 (PD-L1) expression using 5%, 25%, 50% cutoffs in tumor cells (TC) and postsurgical survival in non-small-cell lung cancer (NSCLC) patients. For samples with tumor infiltrating lymphocytes (TIL), correlation between PD-L1 expression in TIL using 1% cutoff and postsurgical survival was also evaluated. Methods: Primary NSCLC tumor surgical samples staging I to IIIA of 126 patients who underwent surgical procedures from September 2009 to August 2012 in Shanghai Chest Hospital, Shanghai Jiao Tong University were retrospectively included...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29187455/comparison-of-pd-l1-mrna-expression-measured-with-the-checkpoint-typer%C3%A2-assay-with-pd-l1-protein-expression-assessed-with-immunohistochemistry-in-non-small-cell-lung-cancer
#9
Ramona Erber, Robert Stöhr, Stefanie Herlein, Claudia Giedl, Ralf Joachim Rieker, Florian Fuchs, Joachim H Ficker, Arndt Hartmann, Elke Veltrup, Ralph M Wirtz, Wolfgang M Brueckl
BACKGROUND: Immunohistochemical (IHC) assessment of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) has become important since the development of anti-PD-1/-PD-L1 directed drugs. Various PD-L1 antibodies and cut-offs have been used in different trials to predict response to these drugs, thus comparison of those studies is difficult. We compared PD-L1 mRNA expression measured by RT-qPCR with PD-L1 protein expression evaluated by IHC. Moreover, we investigated the impact of different tumour tissue acquisition methods on the reliability of PD-L1 measurement techniques...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29181191/anti-pd-1-anti-pd-l1-immunotherapy-versus-docetaxel-for-previously-treated-advanced-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis-of-randomised-clinical-trials
#10
Allan Ramos-Esquivel, Alicia van der Laat, Raquel Rojas-Vigott, Melissa Juárez, Luis Corrales-Rodríguez
Background: To compare the efficacy and toxicity of anti-programmed cell death receptor 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) versus docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). Materials and methods: Phase III randomised clinical trials (RCTs) were identified after systematic review of databases and conference proceedings. A random-effect model was used to determine the pooled HR for overall survival (OS), progression-free survival (PFS) and duration of response...
2017: ESMO Open
https://www.readbyqxmd.com/read/29167005/-distribution-and-clinical-significance-of-ctla-4-pd-1-and-pd-l1-in-peripheral-blood-of-patients-with-small-cell-lung-cancer
#11
Hui Li, Yan Liu, Ying Liu, Jingjing Liu, Dandan Zhao, Ying Wang, Ying Cheng
BACKGROUND: The aim of this study is to explore cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) distribution and clinical value in liquid biopsy (such as blood) of small cell lung cancer (SCLC) patients. METHODS: A total of 60 healthy and 290 chemotherapy-naive patients with SCLC were recruited. Venous blood samples were collected prior to chemotherapy (baseline) and after the second cycle of chemotherapy (2nd cycle), and flow cytometry was used to analyze the level of CTLA-4, PD-1 or PD-L1 with or without CD3, CD4, CD8 or CD25...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29165286/chemoradiation-induced-alteration-of-programmed-death-ligand-1-and-cd8-tumor-infiltrating-lymphocytes-identified-patients-with-poor-prognosis-in-rectal-cancer-a%C3%A2-matched-comparison-analysis
#12
Yu Jin Lim, Jaemoon Koh, Sehui Kim, Sang-Rok Jeon, Eui Kyu Chie, Kyubo Kim, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim, Seung-Yong Jeong, Kyu Joo Park, Hong-Gyun Wu
PURPOSE: To evaluate chemoradiotherapy (CRT)-induced changes in the expression levels of programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) and prognostic associations in rectal cancer. METHODS AND MATERIALS: We performed a paired analysis using pre-CRT biopsies and the corresponding post-CRT resected tissues of 123 rectal cancer patients undergoing preoperative CRT followed by surgery between 2005 and 2012. Immunohistochemistry of PD-L1 and CD8 was analyzed for the specimens...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29163543/interleukin-6-present-in-inflammatory-ascites-from-advanced-epithelial-ovarian-cancer-patients-promotes-tumor-necrosis-factor-receptor-2-expressing-regulatory-t-cells
#13
Nirmala Chandralega Kampan, Mutsa Tatenda Madondo, Orla M McNally, Andrew N Stephens, Michael A Quinn, Magdalena Plebanski
Background: Epithelial ovarian cancer (EOC) remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs) in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2), as well as pro-inflammatory factors such as interleukin 6 (IL-6) and tumor necrosis factor (TNF)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29160310/cyclin-d-cdk4-kinase-destabilizes-pd-l1-via-cul3-spop-to-control-cancer-immune-surveillance
#14
Jinfang Zhang, Xia Bu, Haizhen Wang, Yasheng Zhu, Yan Geng, Naoe Taira Nihira, Yuyong Tan, Yanpeng Ci, Fei Wu, Xiangpeng Dai, Jianping Guo, Yu-Han Huang, Caoqi Fan, Shancheng Ren, Yinghao Sun, Gordon J Freeman, Piotr Sicinski, Wenyi Wei
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit(1,2). However, many cancer patients fail to respond to anti-PD-1/PD-L1 treatment, and the underlying mechanism(s) is not well understood(3-5). Recent studies revealed that response to PD-1/PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells(6,7). Hence, it is important to mechanistically understand the pathways controlling PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1/PD-L1 blockade in cancer patients...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29156738/impact-of-mismatch-repair-deficiency-on-the-colorectal-cancer-immune-microenvironment
#15
Yingyi Zhang, Zhao Sun, Xinxin Mao, Huanwen Wu, Fei Luo, Xi Wu, Liangrui Zhou, Jing Qin, Lin Zhao, Chunmei Bai
Colorectal cancer patients respond inconsistently to immunotherapies, likely due to the immune microenvironments around their tumors. We analyzed the relationship between deficient mismatch repair (dMMR) and the colorectal cancer immune microenvironment to identify predictors of effective immunotherapy. Colorectal cancer patients (n=113) who had undergone surgical resection were divided into dMMR and proficient mismatch repair (pMMR) groups. The levels of immune checkpoint proteins, including programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), indoleamine 2,3 dioxygenase and CD8 were assessed immunohistochemically...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155997/immune-activation-and-benefit-from-avelumab-in-ebv-positive-gastric-cancer
#16
Anshuman Panda, Janice M Mehnert, Kim M Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Michael Kane, Levi Sokol, Mark N Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann W Silk, Joseph Aisner, Nancy Chan, Jyoti Malhotra, Melissa Frankel, Howard L Kaufman, Siraj Ali, Jeffrey S Ross, Eileen P White, Gyan Bhanot, Shridar Ganesan
Response to immune checkpoint therapy can be associated with a high mutation burden, but other mechanisms are also likely to be important. We identified a patient with metastatic gastric cancer with meaningful clinical benefit from treatment with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab. This tumor showed no evidence of high mutation burden or mismatch repair defect but was strongly positive for presence of Epstein-Barr virus (EBV) encoded RNA. Analysis of The Cancer Genome Atlas gastric cancer data (25 EBV+, 80 microsatellite-instable [MSI], 310 microsatellite-stable [MSS]) showed that EBV-positive tumors were MSS...
November 15, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29155514/the-prognostic-effect-of-neoadjuvant-chemoradiotherapy-on-the-change-of-pd-l1-expression-in-patients-with-locally-advanced-rectal-adenocarcinoma
#17
Igor Richter, Tomas Jirasek, Josef Dvorak, Eva Cermakova, Petra Rehakova, Jiri Bartos
PURPOSE: To evaluate the prognostic effect of neoadjuvant chemoradiotherapy on the change of programmed death ligand 1 (PD-L1) expression in patients with locally advanced rectal adenocarcinoma, by comparing PD-L1 expression in pretreatment biopsies and PD-L1 expression in pathological specimens after neoadjuvant chemoradiotherapy. METHODS: A total of 25 patients with rectal adenocarcinoma were evaluated. Patients were treated by neoadjuvant chemoradiotherapy (radiotherapy:44Gy normofraxionation; chemotherapy: capecitabine 825 mg/m(2) in two daily doses)...
July 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29150906/pretreatment-advanced-lung-cancer-inflammation-index-ali-for-predicting-early-progression-in-nivolumab-treated-patients-with-advanced-non-small-cell-lung-cancer
#18
Takayuki Shiroyama, Hidekazu Suzuki, Motohiro Tamiya, Akihiro Tamiya, Ayako Tanaka, Norio Okamoto, Kenji Nakahama, Yoshihiko Taniguchi, Shun-Ichi Isa, Takako Inoue, Fumio Imamura, Shinji Atagi, Tomonori Hirashima
Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes...
November 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#19
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147606/temporal-and-spatial-heterogeneity-of-programmed-cell-death-1-ligand-1-expression-in-malignant-mesothelioma
#20
Simone B S P Terra, Aaron S Mansfield, Haidong Dong, Tobias Peikert, Anja C Roden
Background: Programmed Cell Death 1-Ligand 1 (PD-L1) and Programmed Death Protein 1 (PD-1) blocking antibodies are promising immunotherapies for malignancies. We have previously shown PD-L1 expression in 40% of malignant mesothelioma (MM); however, the temporal and spatial heterogeneity of its expression has not been thoroughly studied. We compared PD-L1 expression between paired primary and metastatic MM. Design: Pathology files (1995-2016) were searched for MM with tissue from multiple sites and/or time points...
2017: Oncoimmunology
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