T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) (TIM-3)

T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a type I transmembrane protein and a key immune checkpoint receptor expressed on Th1 cells, CD8+ cytotoxic T cells, and innate immune cells like NK cells and dendritic cells (UniProt Q8TDQ0). It plays a critical role in regulating adaptive and innate immune responses by inducing T-cell exhaustion and limiting the duration of Th1-mediated immunity (PubMed: 30101380). TIM-3 interacts with several ligands, including Galectin-9, Phosphatidylserine (PtdSer), High Mobility Group Box 1 (HMGB1), and CEACAM1, which trigger inhibitory signals that suppress T-cell proliferation and cytokine production (PubMed: 28211446). In the tumor microenvironment, high expression of TIM-3 is often associated with a state of T-cell dysfunction and poor prognosis across various malignancies, including lung cancer, melanoma, and myeloid leukemias (PubMed: 33451311). Therapeutic strategies focus on using antagonistic monoclonal antibodies to block TIM-3 signaling, often in combination with PD-1/PD-L1 inhibitors, to reinvigorate exhausted T cells and enhance anti-tumor efficacy (ClinicalTrials.gov). Clinical development is ongoing for several TIM-3 targeted agents, such as sabatolimab and cobolimab, primarily aimed at overcoming resistance to existing immunotherapies (PubMed: 34161818).

Other names

Hepatitis A virus cellular receptor 2HAVCR2CD366T-cell immunoglobulin mucin receptor 3TIMD3

Antagonistic monoclonal antibodies block the interaction between TIM-3 and its ligands (such as Galectin-9, PtdSer, HMGB1, and CEACAM1) to prevent inhibitory signaling and restore the effector function of exhausted T cells (PubMed: 30101380).