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TIM3 comes of age as an inhibitory receptor
Open accessAbstract
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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“Nevertheless, tyrosine kinase FYN and human leukocyte antigen B (HLA‐B)‐associated transcript 3 (BAT3) were suggested to inhibit the cytoplasmic tail of TIM‐3 signaling [307, 308, 309].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [307]
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“the latter of which encodes the checkpoint molecule TIM3, one of the most promising new therapeutic approaches in cancer 32 that was recently described in a GWAS as an AD risk gene 2 .”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [32]
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Metadata
- Authors
- Wolf, Y., Anderson, A. C., & Kuchroo, V. K.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Kuchroo, Vijay K.
- Venue
- Nature Reviews Immunology
- Published
- 2019-11-01
- Volume
- 20
- Issue
- 3
- Pages
- 173-185
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- 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
- 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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