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PMID: 25797516 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Overcoming T cell exhaustion in infection and cancer.

Trends in immunology ·Vol. 36 ·No. 4 ·2015-04-00 ·Pages 265-76

Pauken KE, Wherry EJ

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.

Keywords
PD-1 PD-L1 T cell exhaustion cancer chronic infection immunotherapy
MeSH Terms
Animals B7-H1 Antigen/antagonists & inhibitors,immunology Chronic Disease Hepatitis/immunology,pathology,therapy Humans Neoplasms/immunology,pathology,therapy Programmed Cell Death 1 Receptor/antagonists & inhibitors,immunology T-Lymphocytes/immunology
Chemicals
B7-H1 Antigen CD274 protein, human PDCD1 protein, human Programmed Cell Death 1 Receptor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pauken Kristen E
Institute for Immunology and Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104, USA.
Wherry E John
Institute for Immunology and Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104, USA. Electronic address: [email protected].
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Article Info
Journal
Trends in immunology
Abbr.
Trends Immunol
ISSN
1471-4981
DOI
10.1016/j.it.2015.02.008
Email
[email protected]
Published
2015-04-00
Epub
2015-00-18
Pages
265-76
Language
English
Region
England
NLM ID
100966032
PMCID
PMC4393798
Subset
IM
Grants
NIAID NIH HHS · AI112521 · United States
NIAID NIH HHS · AI082630 · United States
NIAID NIH HHS · U19 AI082630 · United States
NIAID NIH HHS · P01 AI112521 · United States
NIAID NIH HHS · AI05343 · United States
NIAID NIH HHS · R01 AI105343 · United States
External Links
PubMed source DOI: 10.1016/j.it.2015.02.008 PMC Full Text View journal details
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