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PD-1 PD-L1

Alessio Cortellini, Melissa Bersanelli, Sebastiano Buti, Elisabetta Gambale, Francesco Atzori, Federica Zoratto, Alessandro Parisi, Davide Brocco, Annagrazia Pireddu, Katia Cannita, Daniela Iacono, Maria R Migliorino, Teresa Gamucci, Michele De Tursi, Tina Sidoni, Maria Tiseo, Maria Michiara, Anselmo Papa, Gesuino Angius, Silverio Tomao, Maria C Fargnoli, Clara Natoli, Corrado Ficorella
AIM: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. MATERIALS & METHODS: We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed...
March 22, 2018: Immunotherapy
M Shao, D H He, Z Cai
No abstract text is available yet for this article.
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Chong Sun, Riccardo Mezzadra, Ton N Schumacher
Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level...
March 20, 2018: Immunity
Nicola Silvestris, Oronzo Brunetti, Rosamaria Pinto, Daniela Petriella, Antonella Argentiero, Livia Fucci, Stefania Tommasi, Katia Danza, Simona De Summa
OBJECTIVES: Adenosquamous cancer of pancreas (ASCP) is a rare variant of pancreatic adenocarcinoma (PDAC). It is characterized by poor prognosis and lacks of literature data supporting the choice of systemic therapies. The role of immunotherapy for this malignancy is still unknown. In this study, we evaluated any differences between immune-related genes of PDAC and its adenosquamous variant with the aim to characterize these histothistotypes and eventually identify potential biomarkers useful for an immune-therapy approach in ASCP...
March 21, 2018: Expert Opinion on Therapeutic Targets
Hiroshi Uchi
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with frequent metastasis and death. MCC has a mortality rate of 30%, making it more lethal than malignant melanoma, and incidence of MCC has increased almost fourfold over the past 20 years in the USA. MCC has long been considered to be an immunogenic cancer because it occurs more frequently in immunosuppressed patients from organ transplant and HIV infection than in those with immunocompetent. Chronic UV light exposure and clonal integration of Merkel cell polyomavirus (MCPyV) are two major causative factors of MCC...
2018: Frontiers in Oncology
Sharon Wei Ling Lee, Giulia Adriani, Erica Ceccarello, Andrea Pavesi, Anthony Tanoto Tan, Antonio Bertoletti, Roger Dale Kamm, Siew Cheng Wong
In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions via PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling. Interestingly, in our 3D static microfluidic model, we observed that monocytes suppressed only retrovirally transduced (Tdx) TCR T cell cytotoxicity toward cancer cells via PD-L1/PD-1, while mRNA electroporated (EP) TCR T cell cytotoxicity was not affected by the presence of monocytes...
2018: Frontiers in Immunology
Anne Mills, Sara Zadeh, Emily Sloan, Zachary Chinn, Susan C Modesitt, Kari L Ring
Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status...
March 20, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Hope S Rugo, Jean-Pierre Delord, Seock-Ah Im, Patrick A Ott, Sarina A Piha-Paul, Phillipe L Bedard, Jasgit Sachev, Christophe Le Tourneau, Emilie M J van Brummelen, Andreea Varga, Roberto Salgado, Sherene Loi, Sanatan Saraf, Dina Pietrangelo, Vassiliki Karantza, Antoinette R Tan
PURPOSE: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor‒positive (ER+)/human epidermal growth factor receptor 2-negative (HER2- ) advanced breast cancer with programmed death ligand 1‒positive (PD-L1‒positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. EXPERIMENTAL DESIGN: Patients with ER+/HER2- advanced breast cancer with PD-L1‒positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
(no author information available yet)
No abstract text is available yet for this article.
March 20, 2018: Cancer Immunology Research
Shinji Yamada, Shunsuke Itai, Mika K Kaneko, Yukinari Kato
Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L1 Mab-4 (IgG2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers...
March 2018: Biochemistry and Biophysics Reports
Qingxia Yao, Karl P Fischer, D Lorne Tyrrell, Klaus S Gutfreund
Programmed death-1 (PD-1), upon engagement by its ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2), provides signals that attenuate adaptive immune responses. Here we describe the identification of the Pekin duck PD-L2 (duPD-L2) and its gene structure. The duPD-L2 cDNA encodes a 321 amino acid protein that has an amino acid identity of 76% and 35% with chicken and human PD-L2, respectively. Mapping of the duPD-L2 cDNA with duck genomic sequences revealed an exonic structure similar to that of the human P dcd1lg2 gene...
March 2018: Biochemistry and Biophysics Reports
Yiming Wang, Rena Ma, Fang Liu, Seul A Lee, Li Zhang
Blockade of programmed death 1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) has been used as cancer immunotherapy in recent years, with the blockade of PD-1 being more widely used than blockade of PD-L1. PD-1 and PD-L1 blockade therapy showed benefits in patients with various types of cancer; however, such beneficial effects were seen only in a subgroup of patients. Improving the efficacy of PD-1 and PD-L1 blockade therapy is clearly needed. In this review, we summarize the recent studies on the effects of gut microbiota on PD-1 and PD-L1 blockade and discuss the new perspectives on improving efficacy of PD-1 and PD-L1 blockade therapy in cancer treatment through modulating gut microbiota...
2018: Frontiers in Immunology
Yu-Tang Chin, Po-Li Wei, Yih Ho, André Wendindondé Nana, Chun A Changou, Yi-Ru Chen, Yu-Chen Sh Yang, Meng-Ti Hsieh, Aleck Hercbergs, Paul J Davis, Ya-Jung Shih, Hung-Yun Lin
Thyroid hormone as L-thyroxine (T4 ), has been shown to promote ovarian cancer cell proliferation via a receptor on plasma membrane integrin αvβ3 to induce the activation of ERK1/2 and expression of programmed death-ligand 1 (PD-L1) in cancer cells. In contrast, resveratrol binds to integrin αvβ3 at a discrete site and induces p53-dependent antiproliferation in malignant neoplastic cells. The mechanism of resveratrol action requires nuclear accumulation of inducible cyclooxygenase (COX)-2 and its complexation with phosphorylated ERK1/2...
March 19, 2018: Endocrine-related Cancer
Linlin Dong, Xiaoyu Zheng, Kun Wang, Guonian Wang, Huichao Zou
BACKGROUND: The T-helper 17 (Th17)/regulatory T (Treg) balance is essential for immune homeostasis. But the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process. METHODS: Mice were divided into Control, Sham and Surgery group randomly. Animals in Surgery group accepted partial gastrectomy...
March 16, 2018: Journal of Trauma and Acute Care Surgery
William Tabayoyong, Jianjun Gao
PURPOSE OF REVIEW: Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research. RECENT FINDINGS: The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity...
March 15, 2018: Current Opinion in Oncology
Junqi Liu, Chuanfeng Zhang, Jiegang Hu, Qing Tian, Xin Wang, Hao Gu, Song Zhang, Di Zhao, Ruitai Fan
Background: Urothelial carcinoma ranks the ninth among malignant cancers. We conducted this study to identify which patients could benefit more from the treatment of programmed death-1 (PD-1)/programmed death-ligand1 (PD-L1) inhibitors. Materials and Methods: We performed literature searches, combined data from qualified literature and performed comparative analyses on the effectiveness of anti-PD-1/PD-L1 antibodies in patients with different PD-L1 expression levels...
February 23, 2018: Oncotarget
Weili Wang, Kuansong Wang, Zihua Chen, Ling Chen, Wei Guo, Ping Liao, Daniel Rotroff, Todd C Knepper, Zhaoqian Liu, Wei Zhang, Howard L Mcleod, Yijing He
Background: Gastric cancer (GC) is a major cause of cancer deaths, especially in Eastern Asia. Current classification systems, including the WHO, Lauren, and TCGA, have clarified the pathological and molecular profiles of GC. However, these classifications lack an association with clinical outcome and guidance for medication selection. Objective: We aimed to identify a new immunoclassification for GC to better predict patient prognosis and aid in patient selection for immunotherapy...
February 23, 2018: Oncotarget
Zilong Hu, Yue Ma, Zhiyang Shang, Shidong Hu, Kai Liang, Wentao Liang, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Monoclonal antibodies recognizing programmed death-ligand 1 (PD-L1) have been used for the clinical treatment of diverse tumor types as a form of immune checkpoint inhibitor, with a favorable therapeutic effect. Dendritic cells (DCs) are potent antigen-presenting cells that serve a pivotal role in the activation of T cells, particularly cytotoxic T lymphocytes (CTLs). DC vaccines loaded with tumor antigens, DC-CTLs and activated T cells have been revealed to be a safe and effective treatment approach against colorectal cancer within a clinical setting...
April 2018: Oncology Letters
Yating Tang, Guang Li, Shan Wu, Lingrong Tang, Ning Zhang, Jinzhao Liu, Shuo Zhang, Lei Yao
Immunotherapy with anti-programmed cell death protein 1 or programmed death ligand 1 (PD-L1) agents has demonstrated promising efficacy for the treatment of various types of malignancies. However, the role of PD-L1 as a tumor prognostic marker remains poorly understood. In the present study, the prognostic value of PD-L1 expression in esophageal carcinoma (EC) following definitive chemoradiotherapy (CRT) was investigated, and its associations with three systemic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were further explored...
April 2018: Oncology Letters
Takaki Akamine, Kazuki Takada, Gouji Toyokawa, Fumihiko Kinoshita, Taichi Matsubara, Yuka Kozuma, Naoki Haratake, Shinkichi Takamori, Fumihiko Hirai, Tetsuzo Tagawa, Tatsuro Okamoto, Yasuto Yoneshima, Isamu Okamoto, Mototsugu Shimokawa, Yoshinao Oda, Yoichi Nakanishi, Yoshihiko Maehara
OBJECTIVES: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients...
March 2018: Surgical Oncology
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