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PD-L1 epigenetic regulation

J Chen, C C Jiang, L Jin, X D Zhang
Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling proteins to cause immune cell dysfunction and apoptosis. One of these inhibitory molecules is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer immunity. Therefore, anti-PD-L1 and anti-PD-1 antibodies have been used for the treatment of cancer, showing promising outcomes...
March 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Aya Shinozaki-Ushiku, Akiko Kunita, Masashi Fukayama
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype that accounts for nearly 10% of gastric carcinomas. EBVaGC is defined by monoclonal proliferation of carcinoma cells with latent EBV infection, as demonstrated by EBV-encoded small RNA (EBER) in situ hybridization. EBVaGC has characteristic clinicopathological features, including predominance among males, a proximal location in the stomach, lymphoepithelioma-like histology and a favorable prognosis. EBVaGC belongs to latency type I or II, in which EBERs, EBNA-1, BARTs, LMP-2A and BART miRNAs are expressed...
April 2015: International Journal of Oncology
Roy S Herbst, Jean-Charles Soria, Marcin Kowanetz, Gregg D Fine, Omid Hamid, Michael S Gordon, Jeffery A Sosman, David F McDermott, John D Powderly, Scott N Gettinger, Holbrook E K Kohrt, Leora Horn, Donald P Lawrence, Sandra Rost, Maya Leabman, Yuanyuan Xiao, Ahmad Mokatrin, Hartmut Koeppen, Priti S Hegde, Ira Mellman, Daniel S Chen, F Stephen Hodi
The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression. These changes distinguish cancer cells from their normal counterparts, allowing tumours to be recognized as foreign by the immune system. However, tumours are rarely rejected spontaneously, reflecting their ability to maintain an immunosuppressive microenvironment. Programmed death-ligand 1 (PD-L1; also called B7-H1 or CD274), which is expressed on many cancer and immune cells, plays an important part in blocking the 'cancer immunity cycle' by binding programmed death-1 (PD-1) and B7...
November 27, 2014: Nature
John Wrangle, Wei Wang, Alexander Koch, Hariharan Easwaran, Helai P Mohammad, Frank Vendetti, Wim Vancriekinge, Timothy Demeyer, Zhengzong Du, Princy Parsana, Kristen Rodgers, Ray-Whay Yen, Cynthia A Zahnow, Janis M Taube, Julie R Brahmer, Scott S Tykodi, Keith Easton, Richard D Carvajal, Peter A Jones, Peter W Laird, Daniel J Weisenberger, Salina Tsai, Rosalyn A Juergens, Suzanne L Topalian, Charles M Rudin, Malcolm V Brock, Drew Pardoll, Stephen B Baylin
Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples...
November 2013: Oncotarget
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