Cited by 4,652T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmune Cell Function and Interaction

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Molecular and cellular insights into T cell exhaustion

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Wherry, E. John, Kurachi, Makoto·2015·Nature Reviews Immunology

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Abstract

In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer.

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Self-citation

Authors: Wherry, E. J., & Kurachi, M.
Affiliations: University of Pennsylvania (US)
Corresponding author: Wherry, E. John
Kurachi, Makoto
ORCID: Wherry, E. John
Kurachi, Makoto
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2015-07-24
Volume: 15
Issue: 8
Pages: 486-499
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri3862
PMC: PMC4889009
OpenAlex: W1910012553
Cited by: 4,652
References: 156
Citations by year: 2026: 563 · 2025: 494 · 2024: 518 · 2023: 508 · 2022: 517 · 2021: 551 · 2020: 441 · 2019: 381 · 2018: 306 · 2017: 227 · 2016: 129 · 2015: 12
FWCI: 21.14
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Public Health Service (HHSN266200500030C)
National Institute of Allergy and Infectious Diseases (HHSN266200500030C, AI 082630, R01AI105343, AI095608, AI105343, AI112521, P01AI112521, U01AI095608, U19AI082630)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords: T cell exhaustion, chronic viral infection, cancer immunotherapy, inhibitory receptors, persistent antigen, inflammatory signals, transcriptional programs, therapeutic target
MeSH terms: Bacterial Infections, Gene Expression Regulation, Humans, Immunologic Memory, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Cytotoxic, Transcription, Genetic, Virus Diseases, Signal Transduction, Cytokines, Clonal Anergy, CD57 Antigens, T-Lymphocytes, Regulatory

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Molecular and cellular insights into T cell exhaustion

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