T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and TAM (Tyro3, Axl, MerTK) family receptors (TIM-3/TAM)

T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and the TAM family (Tyro3, Axl, and MerTK) are distinct but functionally related receptors that regulate immune homeostasis and the tumor microenvironment. TIM-3 is an inhibitory checkpoint receptor expressed on T cells, NK cells, and myeloid cells, where it promotes immune tolerance and T-cell exhaustion upon binding to ligands such as Galectin-9 or phosphatidylserine (UniProt: P0C7P0). The TAM receptors are receptor tyrosine kinases that play a critical role in the phagocytosis of apoptotic cells (efferocytosis) and the dampening of inflammatory responses in innate immune cells (PubMed: 24442144). In many cancers, both TIM-3 and TAM receptors are upregulated, contributing to immune evasion, tumor progression, and resistance to conventional therapies. Therapeutic strategies include monoclonal antibodies designed to block TIM-3 signaling to restore anti-tumor T-cell activity and small molecule inhibitors targeting TAM kinase activity to disrupt oncogenic signaling and suppressive myeloid phenotypes. This entry is marked as incorrect because it combines two distinct protein families—TIM and TAM—into a single target profile, which may require separate clinical and molecular considerations.

Other names

Hepatitis A virus cellular receptor 2HAVCR2CD366TAM receptorsTyro3AxlMerTKTIM familyT-cell membrane protein 3

Drugs targeting this group act via two primary mechanisms: monoclonal antibodies (e.g., Sabatolimab) block the TIM-3 checkpoint receptor to reverse T-cell exhaustion and enhance anti-tumor immunity (PubMed: 30241496), while small molecule inhibitors (e.g., Bemcentinib) target the kinase activity of TAM receptors to inhibit pro-survival signaling in cancer cells and reduce immunosuppressive myeloid activity (Nature Reviews Cancer, 2014).