Mechanism of action of PD-1 receptor/ligand targeted cancer immunotherapy.

European Journal of Immunology
Jannie BorstFerry Ossendorp

Abstract

Immunotherapy targeting the Programmed Death (PD-1) receptor/ligand (L) "checkpoint" rapidly gains ground in the treatment of many cancer types. To increase treatment scope and efficacy, predictive biomarkers and rational selection of co-treatments are required. To meet these demands, we must understand PD-1 function in detail. We here outline recent insights into the regulation of the CD8+ T cell response by PD-1. The prevailing view has been that blockade of PD-1/ligand (L) interaction "reinvigorates" cytotoxic T lymphocytes (CTL) that were rendered dysfunctional in the tumor microenvironment (TME). However, this review stresses that tumors continuously communicate with adjacent draining lymph nodes (LNs) and that the PD-1 checkpoint also operates during T cell priming. We clarify the role of the PD-(L)1 system at the T cell/DC interface, where it regulates T cell receptor (TCR) signaling and CD28 costimulation and thus controls activation of tumor-specific T cells. We also highlight the importance of CD4+ T cell help during priming, which allows DCs to provide other costimulatory and cytokine signals required for optimal CTL differentiation and likely avoidance of a dysfunctional state. Therefore, we pose that PD-(L)1 blocka...Continue Reading

References

Nov 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·T OkazakiT Honjo
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yoshiko IwaiNagahiro Minato
Feb 3, 2005·Nature Immunology·Hans Christian ProbstMaries van den Broek
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Jul 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Li WangRandolph J Noelle
Sep 29, 2009·Nature Immunology·Brian T FifeJeffrey A Bluestone
Jul 5, 2011·Trends in Immunology·Kajsa WingShimon Sakaguchi
May 9, 2014·The Journal of Clinical Investigation·Christian A BauerThorsten R Mempel
Jan 15, 2015·Trends in Immunology·Lucy S K Walker, David M Sansom
Apr 4, 2015·Science·Ton N Schumacher, Robert D Schreiber
Jul 25, 2015·Nature Reviews. Immunology·E John Wherry, Makoto Kurachi
Jan 13, 2016·Proceedings of the National Academy of Sciences of the United States of America·Masahiro KitanoTakaharu Okada
Mar 2, 2016·Annual Review of Immunology·Susanne H BaumeisterArlene H Sharpe
Mar 12, 2016·Cell·A Karolina Palucka, Lisa M Coussens
Jul 28, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicholas M ProvineDan H Barouch
Dec 8, 2016·The Lancet Oncology·Geoffrey T GibneyMichael B Atkins
Jan 20, 2017·Nature·Daniel S Chen, Ira Mellman
Feb 12, 2017·Cell·Padmanee SharmaAntoni Ribas
Apr 28, 2017·Proceedings of the National Academy of Sciences of the United States of America·Alice O KamphorstSuresh S Ramalingam
May 17, 2017·Oncoimmunology·Jan Willem KleinovinkMarieke F Fransen
May 18, 2017·Nature·Mary PhilipAndrea Schietinger
Jan 18, 2018·The Journal of Clinical Investigation·Haidong TangYang-Xin Fu
Jan 18, 2018·The Journal of Clinical Investigation·Heng LinWeiping Zou
Mar 9, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sarah L BuchanAymen Al-Shamkhani
Mar 24, 2018·Science·Antoni Ribas, Jedd D Wolchok
Apr 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Eunseon AhnRafi Ahmed
Jun 7, 2018·Cancer Immunology Research·Apoorvi ChaudhriGordon J Freeman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Vaccines

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