TIM-3, also known as Hepatitis A virus Cell receptor 2 (HAVCR2), is a transmembrane protein and a member of the TIM protein family, which plays a crucial role in immune response regulation. It is expressed on various immune cells, including CD8+ T cells, Th1 cells, regulatory T cells (Tregs), dendritic cells (DCs), natural killer (NK) cells, monocytes, and macrophages. TIM-3 functions as an inhibitory receptor and is associated with T cell exhaustion in chronic infections and cancer. It has been identified as a promising target for cancer immunotherapy, as its blockade can enhance antitumor immunity. The receptor interacts with several ligands, including Galectin-9, CEACAM-1, phosphatidylserine (PtdSer), and High Mobility Group Box 1 (HMGB1). TIM-3 also plays a role in the clearance of apoptotic bodies by interacting with PtdSer on the surface of apoptotic cells. Recent studies have shown that targeting TIM-3 on DCs might be more critical for enhancing antitumor immunity than targeting it on T cells. Furthermore, combined blockade of TIM-3 and PD-1 has shown synergistic effects in reducing tumor growth in various mouse tumor models, suggesting that the combination therapy might be a promising approach for cancer treatment.
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