Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations

Oncogene
Ioannis ZerdesTheodoros Foukakis

Abstract

The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1. Activation of common oncogenic pathways such as JAK/STAT, RAS/ERK, or PI3K/AKT/MTOR, as well as treatment with cytotoxic agents have also been shown to affect tumoral PD-L1 expression. Correlative studies of clinical trials with PD-1/PD-L1 inhibitors have so far shown markedly discordant results regarding the value of PD-L1 expression as a marker of response to treatment. As the indications for immune checkpoint inhibition broaden, understanding the regulation of PD-L1 in cancer will be of utmost importance for defining its role as predictive marker but also for optimizing strategies for cancer immunotherapy. Here, we revi...Continue Reading

References

Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·T S SchaeferD Nathans
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·T OhshimaA B Kulkarni
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·R Dhavan, L H Tsai
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Jul 6, 2002·Science·Meenakshi JainDean W Felsher
Dec 7, 2002·Trends in Biochemical Sciences·Luis Sánchez-PulidoMiguel A Alonso
May 4, 2004·Nature Reviews. Immunology·Lieping Chen
Jan 28, 2005·The Cochrane Database of Systematic Reviews·C CoppinT Wilt
Mar 21, 2007·Methods : a Companion to Methods in Enzymology·Joanne C Cheung, Reinhart A F Reithmeier
May 15, 2007·Oncogene·A S DhillonW Kolch
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Jun 21, 2008·The New England Journal of Medicine·Olivera J Finn
Jul 9, 2008·Cancer Investigation·Yigang QianShusen Zheng
Dec 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michal MarzecMariusz A Wasik
Jan 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ai-Yu GongXian-Ming Chen
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Oct 24, 2009·Nature Reviews. Cancer·Hua YuRichard Jove
Jun 4, 2010·Expert Review of Vaccines·Liubov ZaritskayaAnatoli M Malyguine
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Oct 20, 2010·Cell Division·Terry J Shackleford, Francois X Claret
Sep 1, 2009·Drug Discovery Today. Therapeutic Strategies·Elias UtrerasAshok B Kulkarni
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 25, 2011·Nature Reviews. Cancer·William R Wilson, Michael P Hay
Oct 19, 2011·Journal of Chemotherapy·Wenrong GongXianjin Yi
Nov 23, 2011·Immunology and Cell Biology·Karrune V WoanAlejandro Villagra
Jan 20, 2012·Nature Reviews. Cancer·Neil D Perkins
Jan 25, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael R GreenMargaret A Shipp
Feb 4, 2012·Nature Reviews. Drug Discovery·Lorenzo GalluzziGuido Kroemer
Mar 23, 2012·Immunological Reviews·Joseph A DiDonatoMichael Karin
Jun 23, 2012·Nature Reviews. Cancer·Anna C Belkina, Gerald V Denis
Oct 26, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiaofeng JiangF Stephen Hodi
Sep 24, 2013·JAK-STAT·Antonis E Koromilas, Veronika Sexl

❮ Previous
Next ❯

Citations

Nov 7, 2018·Nature Chemical Biology·Huanbin WangJie Xu
Dec 26, 2018·Clinical and Experimental Immunology·A PawłowskaI Wertel
May 8, 2019·Cancers·Sebastian ChrétienTheodoros Foukakis
Oct 5, 2019·Journal of Clinical Medicine·Valli De ReMaurizio Mascarin
Dec 11, 2019·Cancer Cytopathology·Marc P PusztaszeriFadi Brimo
Apr 3, 2020·Journal of Cellular Physiology·Nirvana Kalantari KhandaniSeyed Isaac Hashemy
Dec 5, 2019·Cancer Immunology, Immunotherapy : CII·Yeni RomeroAnna Zolkiewska
May 30, 2020·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Koji KonoKosaku Mimura
Dec 20, 2018·Cancer Immunology, Immunotherapy : CII·Kathleen M MahoneyGordon J Freeman
May 24, 2019·International Journal of Molecular Sciences·Iris C SalaroglioChiara Riganti
May 22, 2019·Cancers·Phyu P AungJoseph D Khoury
Dec 11, 2019·Journal of Clinical Medicine·Barbara Seliger
Feb 23, 2020·Der Pathologe·Albert RoessnerJohannes Haybäck
Jan 27, 2020·Cancer Immunology, Immunotherapy : CII·Karin SchilbachHisayoshi Hashimoto
Dec 4, 2019·The Chinese Journal of Physiology·G M Shazzad Hossain PrinceMei-Chih Chen
Jul 30, 2020·Annals of Gastroenterological Surgery·Kohei YamashitaHideo Baba
Jan 27, 2019·Cellular Oncology (Dordrecht)·Hara PolioudakiPanayiotis A Theodoropoulos
Dec 19, 2018·Frontiers in Immunology·Martin J RafteryGünther Schönrich
Mar 25, 2020·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Chan Jin YoonJun Hee Woo
Sep 27, 2018·World Journal of Gastroenterology : WJG·Matthias Ocker
Jul 26, 2019·Cancers·Vasileios AtsavesFrancois X Claret
Apr 7, 2019·Nature Biomedical Engineering·Han YaoJie Xu
May 31, 2020·Journal of Clinical Pathology·Ekaterina Olkhov-MitselMichelle R Downes
Nov 12, 2020·ESMO Open·Alexios MatikasTheodoros Foukakis
Dec 2, 2020·International Journal of Molecular Sciences·Kevinn Eddy, Suzie Chen
Jun 23, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexios MatikasTheodoros Foukakis

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
ubiquitination
glycosylation

Clinical Trials Mentioned

NCT02555657
NCT03036488
NCT02954874
NCT03199885
NCT03062358
NCT02702401
NCT03019588
NCT03189719
NCT02564263
NCT02563002

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.