ArticleJournal of immunology (Baltimore, Md. : 1950)2014
T cell Ig and mucin domain-containing protein 3 is recruited to the immune synapse, disrupts stable synapse formation, and associates with receptor phosphatases.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 127 citations in OpenAlex.
- The multifaceted landscape of T cell exhaustion in organ transplantation: From molecular mechanisms (epigenetics, transcription, metabolism) to induction strategies.Genes & diseases · 2026Review
- Review
- TIM-3 in Cardiovascular Disease.Current heart failure reports · 2026Review
- TIM-3 in AML: pathogenic roles and therapeutic targetability.Clinical and experimental medicine · 2026Review
- Immunosuppressive immune microenvironment landscapes in VISTA-high gastric cancer.British journal of cancer · 2026Article
- Unraveling Immune Checkpoint Inhibitor-Associated Cardiovascular Toxicities: Pathway Insights, Mechanisms, and Emerging Therapeutic Targets.Reviews in cardiovascular medicine · 2026Review
- Immune checkpoint TIM-3 in tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- The role of the TIM-3 receptor in inflammatory bowel disease and autoimmunity: implications for TIM-3 and TCR crosstalk.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Fusion protein-mediated costimulation in engineered T cells: from intrinsic signaling to tumor microenvironment rewiring.Frontiers in immunology · 2026Review
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- Review
- New horizons in B-cell lymphoma immunotherapy: From immune checkpoints to precision medicine.Neoplasia (New York, N.Y.) · 2025Review
- Article
- Unraveling the immunomodulatory role of TIM-3 in head and neck squamous cell carcinoma: implications for targeted therapy.Discover oncology · 2025Review
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.Clinical and translational medicine · 2025Review
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies.Cancers · 2025Review
- The Role of TIM-3 in Glioblastoma Progression.Cells · 2025Review
- Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.BMC medical genomics · 2025Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
CD8(+) CTLs are adept at killing virally infected cells and cancer cells and releasing cytokines (e.g., IFN-γ) to aid this response. However, during cancer and chronic viral infections, such as with HIV, this CTL response is progressively impaired due to a process called T cell exhaustion. Previous work has shown that the glycoprotein T cell Ig and mucin domain-containing protein 3 (Tim-3) plays a functional role in establishing T cell exhaustion. Tim-3 is highly upregulated on virus and tumor Ag-specific CD8(+) T cells, and antagonizing Tim-3 helps restore function of CD8(+) T cells. However, very little is known of how Tim-3 signals in CTLs. In this study, we assessed the role of Tim-3 at the immunological synapse as well as its interaction with proximal TCR signaling molecules in primary human CD8(+) T cells. Tim-3 was found within CD8(+) T cell lipid rafts at the immunological synapse. Blocking Tim-3 resulted in a significantly greater number of stable synapses being formed between Tim-3(hi)CD8(+) T cells and target cells, suggesting that Tim-3 plays a functional role in synapse formation. Further, we confirmed that Tim-3 interacts with Lck, but not the phospho-active form of Lck. Finally, Tim-3 colocalizes with receptor phosphatases CD45 and CD148, an interaction that is enhanced in the presence of the Tim-3 ligand, galectin-9. Thus, Tim-3 interacts with multiple signaling molecules at the immunological synapse, and characterizing these interactions could aid in the development of therapeutics to restore Tim-3-mediated immune dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.