Cited by 963Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmune Cell Function and Interaction

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TIM3 comes of age as an inhibitory receptor

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Wolf, Yochai, Anderson, Ana C., Kuchroo, Vijay K.·2020·Nature Reviews Immunology

DOI 10.1038/s41577-019-0224-6PMC PMC7327798

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Abstract

T cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a member of the TIM family, was originally identified as a receptor expressed on interferon-γ-producing CD4+ and CD8+ T cells. Initial data indicated that TIM3 functioned as a 'co-inhibitory' or 'checkpoint' receptor, but due to the lack of a definable inhibitory signalling motif, it was also suggested that TIM3 might act as a co-stimulatory receptor. Recent studies have shown that TIM3 is part of a module that contains multiple co-inhibitory receptors (checkpoint receptors), which are co-expressed and co-regulated on dysfunctional or 'exhausted' T cells in chronic viral infections and cancer. Furthermore, co-blockade of TIM3 and programmed cell death 1 (PD1) can result in tumour regression in preclinical models and can improve anticancer T cell responses in patients with advanced cancers. Here, we highlight the developments in understanding TIM3 biology, including novel ligand identification and the discovery of loss-of-function mutations associated with human disease. In addition, we summarize emerging data from human clinical trials showing that TIM3 indeed acts as a 'checkpoint' receptor and that inhibition of TIM3 enhances the antitumour effect of PD1 blockade.

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Authors: Wolf, Y., Anderson, A. C., & Kuchroo, V. K.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Kuchroo, Vijay K.
ORCID: Wolf, Yochai
Anderson, Ana C.
Kuchroo, Vijay K.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2019-11-01
Volume: 20
Issue: 3
Pages: 173-185
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/s41577-019-0224-6
PMC: PMC7327798
OpenAlex: W2985205513
Cited by: 959
References: 159
Citations by year: 2026: 98 · 2025: 140 · 2024: 191 · 2023: 160 · 2022: 183 · 2021: 142 · 2020: 44
FWCI: 8.75
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (R01CA187975)
National Institute of Allergy and Infectious Diseases (P01AI073748, P01AI056299, P01AI039671)
National Institute of Neurological Disorders and Stroke (R01NS045937)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords: TIM-3, inhibitory receptors, co-inhibitory receptors, immune checkpoint, T cell exhaustion, loss-of-function mutations, antitumor immunity, chronic viral infection, cancer immunotherapy
MeSH terms: Hepatitis A Virus Cellular Receptor 2, Animals, Clinical Trials as Topic, Humans, Signal Transduction, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Programmed Cell Death 1 Receptor

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TIM3 comes of age as an inhibitory receptor

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