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Program death ligand 1/2

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https://www.readbyqxmd.com/read/28223846/prospect-of-the-use-of-checkpoint-inhibitors-in-hepatocellular-cancer-treatments
#1
REVIEW
Ali Raufi, Maria Tria Tirona
Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%-3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28223102/inflammatory-cytokines-il-17-and-tnf-%C3%AE-up-regulate-pd-l1-expression-in-human-prostate-and-colon-cancer-cells
#2
Xun Wang, Lingyun Yang, Feng Huang, Qiuyang Zhang, Sen Liu, Lin Ma, Zongbing You
Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) are co-expressed by T helper 17 (TH17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-α may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells...
February 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28219886/dependence-of-glomerulonephritis-induction-on-novel-intraglomerular-alternatively-activated-bone-marrow-derived-macrophages-and-mac-1-and-pd-l1-in-lupus-prone-nzm2328-mice
#3
Sun-Sang J Sung, Yan Ge, Chao Dai, Hongyang Wang, Shu Man Fu, Rahul Sharma, Young S Hahn, Jing Yu, Thu H Le, Mark D Okusa, Warren K Bolton, Jessica R Lawler
Glomerular damage mediated by glomerulus-infiltrating myeloid-derived cells is a key pathogenic event in lupus nephritis (LN), but the process is poorly understood. Confocal microscopy of kidney sections and flow cytometry analysis of glomerular cells from magnetic bead-purified glomeruli have identified glomerulus-infiltrating leukocyte populations in NZM2328 (NZM) lupus-prone mice with spontaneous chronic glomerulonephritis (GN) and anti-glomerular basement membrane-induced nephritis. The occurrence of a major glomerulus-infiltrating CD11b(+)F4/80(-)I-A(-) macrophage population exhibiting the markers programmed death ligand-1 (PD-L1), Mac-2, and macrophage mannose receptor (CD206) and producing Klf4, Il10, Retnla, Tnf, and Il6 mRNA, which are known to be expressed by alternatively activated (M2b) macrophages, correlated with proteinuria status...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219001/glut1-as-a-prognostic-factor-for-classical-hodgkin-s-lymphoma-correlation-with-pd-l1-and-pd-l2-expression
#4
Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
Background: Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin's lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL...
February 21, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#5
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28212990/high-plasma-levels-of-soluble-programmed-cell-death-ligand-1-are-prognostic-for-reduced-survival-in-advanced-lung-cancer
#6
Yusuke Okuma, Yukio Hosomi, Yoshiro Nakahara, Kageaki Watanabe, Yukiko Sagawa, Sadamu Homma
OBJECTIVES: Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancer patients remain unknown. PATIENTS AND METHODS: Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212060/pembrolizumab-as-second-line-therapy-for-advanced-urothelial-carcinoma
#7
Joaquim Bellmunt, Ronald de Wit, David J Vaughn, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J Vogelzang, Miguel A Climent, Daniel P Petrylak, Toni K Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stéphane Culine, Cora N Sternberg, Yabing Mai, Christian H Poehlein, Rodolfo F Perini, Dean F Bajorin
Background Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. Methods In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine...
February 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28207525/plasma-levels-of-soluble-programmed-death-ligand-1-may-be-associated-with-overall-survival-in-nonsmall-cell-lung-cancer-patients-receiving-thoracic-radiotherapy
#8
Jing Zhao, Peng Zhang, Jianhua Wang, Qingsong Xi, Xueqi Zhao, Minghua Ji, Guangyuan Hu
Immune-checkpoint signaling plays an important role in immunosuppression of tumors. We aimed to investigate the association of soluble programmed death-ligand 1 (sPD-L1) level in plasma with overall survival (OS) in locally advanced or inoperable nonsmall-cell lung cancer (NSCLC) patients treated with thoracic radiotherapy (TRT). We used ELISA to evaluate the sPD-L1 levels at diagnosis and during TRT in 126 clinically inoperable NSCLC patients. OS rates were followed up and recorded. SPSS software and GraphPad Prism 5 were used for statistics...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28188721/pd-l1-over-expression-is-associated-with-a-poor-prognosis-in-asian-non-small-cell-lung-cancer-patients
#9
Haifeng Xia, Ji Shen, Fang Hu, Shaomu Chen, Haitao Huang, Yaozeng Xu, Haitao Ma
BACKGROUND: The prognostic role of programmed cell death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis was conducted to clarify the association of PD-L1 with survival in NSCLC patients. METHODS: Relevant studies were collected from PubMed, Embase and Web of Science. Only studies in which PD-L1 expression was detected by immunohistochemical staining in NSCLC patients correlated with patient survival data were included...
February 7, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28188133/pd1-blockade-with-pembrolizumab-is-highly-effective-in-relapsed-or-refractory-nk-t-cell-lymphoma-failing-l-asparaginase
#10
Yok-Lam Kwong, Thomas S Y Chan, Daryl Tan, Seok Jin Kim, Li-Mei Poon, Benjamin Mow, Pek-Lan Khong, Florence Loong, Rex Au-Yeung, Jabed Iqbal, Colin Phipps, Eric Tse
Natural killer (NK)/T-cell lymphomas failing L-asparaginse-regimens have no known salvage and are almost invariably fatal. Seven male NK/T-cell lymphoma patients (age: 49, 31-68, years) failing 2 (1-5) regimens (including L-asparaginase-regimens, and allogeneic hematopoietic stem cell transplantation, HSCT, in 2 cases), were treated with the anti-programmed-death-1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic and molecular (circulating Epstein-Barr virus, EBV, DNA) criteria...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#11
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28181012/oral-administration-of-the-lactic-acid-bacterium-pediococcus-acidilactici-attenuates-atherosclerosis-in-mice-by-inducing-tolerogenic-dendritic-cells
#12
Taiji Mizoguchi, Kazuyuki Kasahara, Tomoya Yamashita, Naoto Sasaki, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Tomohiro Hayashi, Naoki Kitano, Naofumi Yoshida, Hilman Zulkifli Amin, Ken-Ichi Hirata
The intestinal microbiota appears to play an important role in the development of atherosclerosis. We investigated the effect of the probiotic lactic acid bacterium Pediococcus acidilactici R037 on atherosclerosis using apolipoprotein E-deficient (ApoE (-/-)) mice. Six-week-old ApoE (-/-) mice were orally administered R037 six times a week. Mice treated with R037 for 12 weeks exhibited markedly attenuated atherosclerotic lesions in the aortic root (2.3 ± 0.15 × 10(5) µm(2) vs. 3.3 ± 0.29 × 10(5) µm(2), respectively; P < 0...
February 8, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28169111/expression-pattern-of-immune-checkpoint-associated-molecules-in-radical-nephrectomy-specimens-as-a-prognosticator-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors
#13
Takuto Hara, Hideaki Miyake, Masato Fujisawa
OBJECTIVE: To analyze the expression pattern of immune checkpoint-associated molecules in tumor tissues to determine the prognostic significance of these molecules in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). METHODS: Radical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining...
February 3, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28159587/evaluation-of-hla-g-hla-e-and-pd-l1-proteins-in-oral-osteosarcomas
#14
Diego Antonio Costa Arantes, Andréia Souza Gonçalves, Bruno Correia Jham, Eliza Carla Barroso Duarte, Élbio Candido de Paula, Henrique Moura de Paula, Elismauro Francisco Mendonça, Aline Carvalho Batista
OBJECTIVE: The aim of this study was to investigate the expression of human leukocyte antigens (HLAs) G and E and programmed death-ligand 1 (PD-L1) in oral osteosarcoma (OO) (n = 13). The relationship between the expression of these molecules and histologic grading and metastasis was also evaluated. STUDY DESIGN: HLA-G, HLA-E, and PD-L1 were identified by immunohistochemistry. Samples of normal bone tissue (n = 6) were used as controls. The sections were evaluated using a semiquantitative scoring system with an immunoreactive score, where a score of 0 was considered absent, ≤2 was low, and >2 was high expression...
December 14, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28156542/the-level-of-soluble-programmed-death-ligand-1-in-lung-cancer-an-exploratory-biomarker-study
#15
Li Pan, Sutang Guo, Jiexian Jing, Xu Dong Zhang, Xia Song
: 249 Background: A new approach to immunotherapy based on programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1) pathway represents a remarkable innovation in lung cancer treatment. There is growing evidence that lung cancer cells exploit the PD-L1 to cause local immune-suppression. The aim of this prospective study was to investigate the prevalence and prognostic roles of soluble PD-L1 (sPD-L1) protein in the blood of patients with lung cancer. METHODS: A total of 159 patients with lung cancer who were diagnosed by histopathology or cytopathology between July 2013 and October 2015 were enrolled...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28153603/high-programmed-death-1-expression-on-t-cells-in-aplastic-anemia
#16
Wanhong Zhao, Yilin Zhang, Pengyu Zhang, Juan Yang, Longjin Zhang, Aili He, Wanggang Zhang, Tamura Hideto
Programmed death 1 (PD-1) has been reported to be associated with aberrant regulation of T cells activation in aplastic anemia (AA). However, the connection between PD-1 expression status and AA needs to be further explored. The aim of this study is to investigate PD-1 expression status on T cells in AA patients and to explore the effect of PD-1 on apoptosis of T cells and BMHSCs. The concentration of platelet, lymphocyte and hemoglobin in peripheral blood of AA patients and healthy volunteers was detected by automatic blood-counter system...
January 30, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28132868/lag-3-protein-expression-in-non-small-cell-lung-cancer-and-its-relationship-with-pd-1-pd-l1-and-tumor-infiltrating-lymphocytes
#17
Yayi He, Hui Yu, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafal Dziadziuszko, Kenichi Suda, Shengxiang Ren, Chunyan Wu, Likun Hou, Caicun Zhou, Fred R Hirsch
BACKGROUND: Immunotherapy targeting the programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) checkpoint has shown promising efficacy in patients with non-small cell lung cancer (NSCLC). Lymphocyte activation gene-3 (LAG-3) is another important checkpoint, and its role in NSCLC is still not clear. In this study, we investigated LAG-3 protein expression and its correlation with PD-1, PD-L1, tumor-infiltrating lymphocytes (TILs), and association with survival in NSCLC. METHODS: The expression of LAG-3 (EPR4392, Abcam) protein was assessed in 55 NSCLC cell lines by immunohistochemistry (IHC)...
January 26, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28132417/noncoding-rnas-and-immune-checkpoints-clinical-implications-as-cancer-therapeutics
#18
REVIEW
Maria A Smolle, Horatiu N Calin, Martin Pichler, George A Calin
A major mechanism of tumor development and progression is silencing of the patient's immune response to cancer-specific antigens. Defects in the so-called cancer immunity cycle may occur at any stage of tumor development. Within the tumor microenvironment, aberrant expression of immune checkpoint molecules with activating or inhibitory effects on T lymphocytes induces immune tolerance and cellular immune escape. Targeting immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and its ligand PD-L1 with specific antibodies has proven to be a major advance in the treatment of several types of cancer...
January 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28111882/programmed-death-ligand-1-is-expressed-in-canine-b-cell-lymphoma-and-downregulated-by-mek-inhibitors
#19
S R Kumar, D Y Kim, C J Henry, J N Bryan, K L Robinson, A M Eaton
Programmed death ligand 1 (PD-L1) expression in antigen-presenting cells and tumors can inhibit T cell-mediated immunity. In this study, PD-L1 mRNA and protein expression was evaluated in canine B cell lymphoma (CLL17-71), large T-cell leukemia (CLGL-90), B cell leukemia (GL-1) and primitive leukocyte round cell neoplasia (CLL-1390). Variable PD-L1 mRNA and protein were observed in these cells with high endogenous expression present in CLL17-71 cells. PD-L1 protein was also observed in canine patient B cell lymphoma tissues using immunostaining...
January 22, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#20
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
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