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Program death ligand 1/2

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https://www.readbyqxmd.com/read/28430626/expression-of-pd-l1-and-prognosis-in-breast-cancer-a-meta-analysis
#1
Minghui Zhang, Houbin Sun, Shu Zhao, Yan Wang, Haihong Pu, Yan Wang, Qingyuan Zhang
The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest. However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to assess the association between PD-L1 protein expression and clinicopathological features and the impact of this relationship on breast cancer survival. We performed a systematic search of the PubMed, EMBASE, and Cochrane Library databases to determine the correlations among PD-L1 expression, clinicopathological features and overall survival (OS)...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424325/fda-approval-summary-atezolizumab-for-the-treatment-of-patients-with-progressive-advanced-urothelial-carcinoma-after-platinum-containing-chemotherapy
#2
Yang-Min Ning, Daniel Suzman, V Ellen Maher, Lijun Zhang, Shenghui Tang, Tiffany Ricks, Todd Palmby, Wentao Fu, Qi Liu, Kirsten B Goldberg, Geoffrey Kim, Richard Pazdur
Until recently in the United States, no products were approved for second-line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Atezolizumab is a programmed death-ligand 1 (PD-L1) blocking antibody and represents the first approved product directed against PD-L1...
April 19, 2017: Oncologist
https://www.readbyqxmd.com/read/28423587/the-correlation-between-programmed-death-ligand-1-expression-and-driver-gene-mutations-in-nsclc
#3
Haitao Yang, Huijuan Chen, Shuimei Luo, Lina Li, Sijing Zhou, Ruifen Shen, Heng Lin, Xianhe Xie
OBJECTIVES: This study aimed to evaluate the correlation between positive PD-L1 expression and driver gene mutations in NSCLC and to seek preliminary evidence in favor of the strategy of PD-L1 inhibitors plus targeted agents. RESULTS: The overall analyses revealed that positive PD-L1 expression had a significant relationship with KRAS status (RR = 1.26; 95% CI, 1.06-1.50, P = 0.010), but no correlation with clinical characteristics (gender, smoking status, histological types), driver gene status (EGFR, ALK) and overall survival (OS): male versus female (RR = 1...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416578/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#4
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
April 17, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28416123/immune-checkpoint-inhibitors-for-patients-with-advanced-non-small-cell-lung-cancer-a%C3%A2-systematic-review
#5
REVIEW
Peter M Ellis, Emily T Vella, Yee C Ung
Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC...
February 16, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28414296/pd-l1-interacts-with-cd80-to-regulate-graft-versus-leukemia-activity-of-donor-cd8-t-cells
#6
Xiong Ni, Qingxiao Song, Kaniel Cassady, Ruishu Deng, Hua Jin, Mingfeng Zhang, Haidong Dong, Stephen Forman, Paul J Martin, Yuan-Zhong Chen, Jianmin Wang, Defu Zeng
Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and the immunostimulatory molecule CD80 and functions as a checkpoint to regulate immune responses. The interaction of PD-L1 with CD80 alone has been shown to exacerbate the severity of graft-versus-host disease (GVHD), whereas costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that temporary depletion of donor CD4+ T cells early after hematopoietic cell transplantation effectively prevents GVHD while preserving strong graft-versus-leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28412591/baseline-%C3%AE-catenin-programmed-death-ligand-1-expression-and-tumour-infiltrating-lymphocytes-predict-response-and-poor-prognosis-in-braf-inhibitor-treated-melanoma-patients
#7
Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BACKGROUND: The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome...
April 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28408783/prokaryotic-expression-of-the-extracellular-domain-of-porcine-programmed-death-1-pd-1-and-its-ligand-pd-l1-and-identification-of-the-binding-with-peripheral-blood-mononuclear-cells-in-vitro
#8
Yan-Ping Zhu, Feng Yue, Yong He, Peng Li, Yuan Yang, Yu-Ting Han, Yan-Fang Zhang, Guo-Peng Sun, Dong-Guang Guo, Mei Yin, Xuan-Nian Wang
Programmed cell death protein 1 (PD-1), a costimulatory molecule of the CD28 family, has 2 ligands, PD-L1 and PD-L2. Our previous studies showed that the expression of PD-1 and PD-L1 is up-regulated during viral infection in pigs. Extensive studies have shown that blockade of the PD-1/PD-L1 pathways by anti-PD-L1 antibody or soluble PD-1 restores exhausted T-cells in humans and mice. In the present study the extracellular domains of PD-1 and PD-L1 were used to evaluate the binding of PD-1 and PD-L1 with peripheral blood mononuclear cells (PBMCs)...
April 2017: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
https://www.readbyqxmd.com/read/28407528/immunotherapy-revolutionises-non-small-cell-lung-cancer-therapy-results-perspectives-and-new-challenges
#9
REVIEW
Etienne Giroux Leprieur, Coraline Dumenil, Catherine Julie, Violaine Giraud, Jennifer Dumoulin, Sylvie Labrune, Thierry Chinet
Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10...
April 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28407039/tumor-immune-microenvironment-and-nivolumab-efficacy-in-egfr-mutation-positive-non-small-cell-lung-cancer-based-on-t790m-status-after-disease-progression-during-egfr-tki-treatment
#10
K Haratani, H Hayashi, T Tanaka, H Kaneda, Y Togashi, K Sakai, K Hayashi, S Tomida, Y Chiba, K Yonesaka, Y Nonagase, T Takahama, J Tanizaki, K Tanaka, T Yoshida, K Tanimura, M Takeda, H Yoshioka, T Ishida, T Mitsudomi, K Nishio, K Nakagawa
Background.: The efficacy of programmed death-1 (PD-1) blockade in epidermal growth factor receptor gene ( EGFR ) mutation-positive non-small cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR . Patients and Methods.: We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A)...
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28406723/aspirin-use-and-colorectal-cancer-survival-according-to-tumor-cd274-programmed-cell-death-1-ligand-1-expression-status
#11
Tsuyoshi Hamada, Yin Cao, Zhi Rong Qian, Yohei Masugi, Jonathan A Nowak, Juhong Yang, Mingyang Song, Kosuke Mima, Keisuke Kosumi, Li Liu, Yan Shi, Annacarolina da Silva, Mancang Gu, Wanwan Li, NaNa Keum, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Edward L Giovannucci, Marios Giannakis, Scott J Rodig, Gordon J Freeman, Daniel Nevo, Molin Wang, Andrew T Chan, Charles S Fuchs, Reiko Nishihara, Shuji Ogino
Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell-mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. We hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway...
April 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28404866/combined-antiangiogenic-and-anti-pd-l1-therapy-stimulates-tumor-immunity-through-hev-formation
#12
Elizabeth Allen, Arnaud Jabouille, Lee B Rivera, Inge Lodewijckx, Rindert Missiaen, Veronica Steri, Kevin Feyen, Jaime Tawney, Douglas Hanahan, Iacovos P Michael, Gabriele Bergers
Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ-expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28404865/dual-angiopoietin-2-and-vegfa-inhibition-elicits-antitumor-immunity-that-is-enhanced-by-pd-1-checkpoint-blockade
#13
Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Pathological angiogenesis is a hallmark of cancer and a therapeutic target. Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a bispecific antibody (A2V) provided superior therapeutic benefits, as compared to the single agents, in both genetically engineered and transplant tumor models, including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor (RIP1-Tag2), and melanoma...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28403071/the-expression-and-clinical-relevance-of-pd-1-pd-l1-and-tp63-in-patients-with-diffuse-large-b-cell-lymphoma
#14
Xia Fang, Bing Xiu, Zhizhang Yang, Weizhe Qiu, Long Zhang, Suxia Zhang, Yunjin Wu, Xuyou Zhu, Xue Chen, Suhong Xie, Xianghua Yi, Aibin Liang, Yu Zeng
Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28401366/resistance-to-immunotherapy-clouds-in-a-bright-sky
#15
REVIEW
Gérard Milano
Two major challenges persist for an optimal management of immunotherapy: i) identifying those patients who will benefit from this type of therapy, and ii) determining the biological, cellular and molecular mechanisms that trigger disease progression while on therapy. There is a consensual view in favor of standardizing practices currently used to measure programmed death ligand 1 (PD-L1) expression that relates to innate resistance. The tumor mutation landscape has been widely explored as a potential predictor of treatment efficacy...
April 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28387723/classical-and-novel-tspo-ligands-for-the-mitochondrial-tspo-can-modulate-nuclear-gene-expression-implications-for-mitochondrial-retrograde-signaling
#16
Nasra Yasin, Leo Veenman, Sukhdev Singh, Maya Azrad, Julia Bode, Alex Vainshtein, Beatriz Caballero, Ilan Marek, Moshe Gavish
It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 min, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression...
April 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28375787/avelumab-an-anti-programmed-death-ligand-1-antibody-in-patients-with-refractory-metastatic-urothelial-carcinoma-results-from-a-multicenter-phase-ib-study
#17
Andrea B Apolo, Jeffrey R Infante, Ani Balmanoukian, Manish R Patel, Ding Wang, Karen Kelly, Anthony E Mega, Carolyn D Britten, Alain Ravaud, Alain C Mita, Howard Safran, Thomas E Stinchcombe, Marko Srdanov, Arnold B Gelb, Michael Schlichting, Kevin Chin, James L Gulley
Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1...
April 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28371827/mutational-burden-immune-checkpoint-expression-and-mismatch-repair-in-glioma-implications-for-immune-checkpoint-immunotherapy
#18
Tiffany R Hodges, Martina Ott, Joanne Xiu, Zoran Gatalica, Jeff Swensen, Shouhao Zhou, Jason T Huse, John de Groot, Shulin Li, Willem W Overwijk, David Spetzler, Amy B Heimberger
Background.: Despite a multiplicity of clinical trials testing immune checkpoint inhibitors, the frequency of expression of potential predictive biomarkers is unknown in glioma. Methods.: In this study, we profiled the frequency of shared biomarker phenotypes. To clarify the relationships among tumor mutational load (TML), mismatch repair (MMR), and immune checkpoint expression, we profiled patients with glioma (n = 327), including glioblastoma (GBM) (n = 198), whose samples had been submitted for analysis from 2009 to 2016...
March 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28363612/programmed-death-ligand-1-expression-distinguishes-invasive-encapsulated-follicular-variant-of-papillary-thyroid-carcinoma-from-noninvasive-follicular-thyroid-neoplasm-with-papillary-like-nuclear-features
#19
Guodong Fu, Olena Polyakova, Christina MacMillan, Ranju Ralhan, Paul G Walfish
BACKGROUND: The noninvasive Encapsulated follicular variant of papillary thyroid cancer (EFVPTC) has been reclassified as Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) without a significant risk for malignant behavior. However the evaluation remains a challenge for clinicians. We sought to determine whether programmed death-ligand 1 (PD-L1) expression may serve as a biomarker to predict invasiveness of EFVPTC and assist to distinguish these neoplasms from NIFTP...
March 24, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28350690/programmed-death-1-pathway-in-orbital-invasion-of-cutaneous-carcinomas
#20
Edward J Wladis, Joshua A Lee, J Andrew Carlson, Nina Martino, Alejandro P Adam
PURPOSE: The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit. METHODS: Immunohistochemical staining for the programmed death-1 receptor and ligand was performed on exenteration specimens of invasive cutaneous orbital malignancies (n = 12) and nodular basal cell carcinoma (n = 10)...
March 27, 2017: Ophthalmic Plastic and Reconstructive Surgery
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