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

T-cell immunoglobulin and mucin domain–containing protein 3 receptor (TIM-3, also known as HAVCR2) is a type I transmembrane glycoprotein in the immunoglobulin superfamily, structurally characterized by an N-terminal IgV-like domain, a mucin-like domain, a transmembrane region, and a cytoplasmic tail with multiple conserved tyrosine residues[5][3][4]. TIM-3 is expressed on a variety of immune cells, including CD4+ and CD8+ T cells, regulatory T cells, natural killer (NK) cells, dendritic cells, monocytes, macrophages, and mast cells[1][5][4][6]. Functionally, it acts primarily as an inhibitory receptor, negatively regulating T cell activation and cytokine production, contributing to immune cell exhaustion in chronic infection and cancer settings, and maintaining peripheral tolerance[2][5][4]. TIM-3 ligands include galectin-9, CEACAM1, phosphatidylserine, and HMGB1, and engagement of TIM-3 can induce T cell apoptosis or functional exhaustion[5][4]. It is a key immune checkpoint and a promising target for therapeutic intervention in cancers, as well as a potential marker for disease progression or treatment response[1][8]. Experimental TIM-3 antagonists are under clinical investigation for reversing immune exhaustion and enhancing anti-tumor responses, particularly in combination with other immunotherapies such as anti-PD-1/PD-L1 agents; safety challenges primarily relate to immune-related adverse effects associated with excessive immune activation[1][8][4].

Other names

Hepatitis A virus cellular receptor 2 (HAVCR2)T cell immunoglobulin and mucin-domain containing-3TIM3TIM-3 receptorHAVcr-2

Immune checkpoint blockade to enhance anti-tumor immunity[1][8]; Antagonism of TIM-3 inhibits its negative regulatory signals, resulting in increased T cell proliferation and effector function[4][8]; Co-blockade (with anti-PD-1/PD-L1) to overcome immune resistance in cancer immunotherapy[8][5]