The DOI matches its Crossref record; 157 of the 159 references it cites were found in a registry or an index.
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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Cites
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Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation
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Self-citationMiller, B. C., Sen, D. R., Al Abosy, R., Bi, K., Virkud, Y. V., LaFleur, M. W., Yates, K. B., Lako, A., Felt, K., Naik, G. S., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0312-6 · Cited by 2,087
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072
Self-citationDefining CD8+ T cells that provide the proliferative burst after PD-1 therapy
Im, S. J., Hashimoto, M., Gerner, M. Y., Lee, J., Kissick, H. T., Burger, M. C., Shan, Q., Hale, J. S., Lee, J., Nasti, T. H., et al. (2016) · Nature · doi:10.1038/nature19330 · Cited by 2,070
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity
Zhu, C., Anderson, A. C., Schubart, A., Xiong, H., Imitola, J., Khoury, S. J., Zheng, X. X., Strom, T. B., & Kuchroo, V. K. (2005) · Nature Immunology · doi:10.1038/ni1271 · Cited by 2,057
Self-citationDefining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
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Research works printed but not linked: 2
- Weiss, G. J. et al. A phase 1 study of TSR-022, an anti-TIM-3 monoclonal antibody, in patients (pts) with advanced solid tumors. J. Immunother. Cancer 5, 86 (2017).
- Davar, D. et al. A phase 1 study of TSR-022, an anti-TIM-3 monoclonal antibody, in combination with TSR-042 (anti-PD-1) in patients with colorectal cancer and post-PD-1 NSCLC and melanoma. J. Immunother. Cancer 6, 115 (2018).
Cited by
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Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways
Kraehenbuehl, L., Weng, C., Eghbali, S. Z., Wolchok, J. D., & Merghoub, T. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00552-7 · Cited by 885
The future of cancer immunotherapy: microenvironment-targeting combinations
Murciano‐Goroff, Y. R., Warner, A. B., & Wolchok, J. D. (2020) · Cell Research · doi:10.1038/s41422-020-0337-2 · Cited by 768
Glioma targeted therapy: insight into future of molecular approaches
Yang, K., Wu, Z., Zhang, H., Zhang, N., Wu, W., Wang, Z., Dai, Z., Zhang, X., Zhang, L., Peng, Y., et al. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01513-z · Cited by 738
Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W., Hsu, J.-M., Cha, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21099-2 · Cited by 656
Baessler, A., & Vignali, D. A. A. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-110914 · Cited by 420
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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