Overcoming T cell exhaustion in infection and cancer

Trends in Immunology
Kristen E Pauken, E John Wherry

Abstract

Inhibitors of the Programmed Cell Death 1: Programmed Cell Death 1 ligand 1 (PD-1:PD-L1) pathway, a central regulator of T cell exhaustion, have been recently shown to be effective for treatment of different cancers. However, clinical responses are mixed, highlighting the need to better understand the mechanisms of action of PD-1:PD-L1, the role of this pathway in immunity to different tumors, and the molecular and cellular effects of PD-1 blockade. Here, we review the molecular regulation of T cell exhaustion, placing recent findings on PD-1 blockade therapies in cancer in the context of the broader understanding of the roles of the PD-1:PD-L1 pathway in T cell exhaustion during chronic infection. We discuss the current understanding of the mechanisms involved in reversing T cell exhaustion, and outline critical areas of focus for future research, both basic and clinical.

References

Dec 22, 1998·The Journal of Experimental Medicine·A J ZajacR Ahmed
May 3, 2000·The Journal of Experimental Medicine·F LechnerB D Walker
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yoshiko IwaiNagahiro Minato
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Annette OxeniusRodney E Phillips
Apr 3, 2003·Immunological Reviews·Leonard J Appleman, Vassiliki A Boussiotis
Apr 22, 2003·Nature Medicine·Tyler J CurielWeiping Zou
Oct 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·E John WherryRafi Ahmed
Oct 18, 2005·Molecular and Cellular Biology·Richard V ParryJames L Riley
Nov 3, 2005·Nature Clinical Practice. Oncology·Steven A Rosenberg
Nov 8, 2005·Nature Immunology·Andrew M IntlekoferSteven L Reiner
Oct 17, 2006·Nature Medicine·David G BrooksMichael B A Oldstone
Apr 11, 2007·The Journal of Experimental Medicine·Haina ShinE John Wherry
Aug 19, 2007·The Journal of Experimental Medicine·Andrew M IntlekoferSteven L Reiner
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Apr 2, 2008·Nature Reviews. Immunology·Reinhold FörsterAntal Rot
Sep 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shawn D BlackburnE John Wherry
Dec 23, 2008·Immunity·Charles D Surh, Jonathan Sprent
May 9, 2009·Science·Heidi ElsaesserDavid G Brooks
May 12, 2009·Immunological Reviews·James L Riley
Aug 12, 2009·The Prostate·Karen S SfanosCharles G Drake

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Citations

Feb 13, 2016·Biochimica Et Biophysica Acta·Fernando MendesManuel Santos Rosa
Aug 28, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kristian TaipaleAkseli Hemminki
Oct 21, 2015·Vaccine·Michael A Morse, H Kim Lyerly
Aug 11, 2015·Molecular Immunology·Greg M Delgoffe, Jonathan D Powell
Nov 22, 2015·Seminars in Immunology·Peter KaragiannisShin Kaneko
Jul 15, 2015·Trends in Pharmacological Sciences·Jordan M ChinaiXingxing Zang
Jul 15, 2015·Trends in Immunology·Shivani Srivastava, Stanley R Riddell
Jul 25, 2015·Nature Reviews. Immunology·E John Wherry, Makoto Kurachi
Jun 19, 2015·Cell Death & Disease·Y JiangB Zhu
Feb 5, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Roy M BremnesTom Dønnem
Mar 17, 2015·Trends in Immunology·Peter J Siska, Jeffrey C Rathmell
Apr 26, 2016·Nature Structural & Molecular Biology·Kathryn M HastieErica Ollmann Saphire
May 6, 2016·Expert Review of Respiratory Medicine·Mariacarmela SantarpiaRafael Rosell
Jun 18, 2016·Journal of Immunology Research·John Reiser, Arnob Banerjee
May 25, 2016·Trends in Immunology·Paul E HughesLawren C Wu
Jan 6, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A Sanchez-Fueyo, J F Markmann
May 28, 2016·European Journal of Immunology·Pranay DograBen Youngblood
Jun 9, 2016·European Journal of Immunology·Marie BettonvilleMichel Y Braun
Aug 3, 2016·The Journal of Experimental Medicine·SuJin HwangImtiaz A Khan
Aug 9, 2016·Expert Review of Vaccines·Teilo H Schaller, John H Sampson
Oct 16, 2016·Clinics in Liver Disease·Bertram Bengsch, Kyong-Mi Chang
Aug 16, 2016·The Journal of Clinical Investigation·Adil I DaudMichael D Rosenblum
Jul 28, 2016·The Journal of Experimental Medicine·Daniel T UtzschneiderDietmar Zehn
Oct 22, 2016·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Zachary R Healy, David M Murdoch
Oct 17, 2016·Current Opinion in Immunology·Eoin F McKinney, Kenneth Gc Smith
Oct 23, 2016·Archives of Pharmacal Research·Junsik ParkEui-Cheol Shin
Nov 2, 2016·Critical Reviews in Microbiology·Nargis KhanJaved Naim Agrewala
Nov 12, 2016·Cancer Gene Therapy·D D GeorgeS C Katz
Sep 1, 2016·Immunology and Cell Biology·Eoin F McKinney, Kenneth Gc Smith
Nov 26, 2016·Cancers·Smitha MenonGrace Dy

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