T cell immunoglobulin and ITIM domain (TIGIT)

TIGIT is a transmembrane glycoprotein receptor belonging to the immunoglobulin superfamily. It is expressed on various lymphocyte subsets, including CD8+ T cells, memory and regulatory CD4+ T cells, and NK cells. TIGIT binds to members of the nectin family, with CD155 (PVR) being its main functional ligand. TIGIT functions as an inhibitory immune checkpoint, suppressing T cell and NK cell activity and promoting tolerogenic dendritic cell phenotypes. It plays a key role in immune regulation and has emerged as a promising therapeutic target in cancer.

Other names

VSIG9VSTM3WUCAMT-cell immunoreceptor with Ig and ITIM domains

TIGIT functions as an inhibitory immune checkpoint through multiple mechanisms: Cell-Intrinsic Inhibition: - Directly delivers inhibitory signals to effector lymphocytes upon ligand binding. - Inhibits T cell proliferation and function by attenuating TCR-driven activation signals. - Suppresses NK cell degranulation, cytokine production, and cytotoxicity against tumor targets expressing its ligands. Cell Extrinsic Effects: - Acts as a ligand for receptors on antigen-presenting cells such as dendritic cells. - Engagement induces tolerogenic dendritic cell phenotypes—decreased IL‑12 production/increased IL‑10 secretion—thereby dampening priming of anti-tumor responses. Regulatory Function in Tregs: - Enhances suppressive activity of regulatory T cells. - Upregulation in tumor-infiltrating or natural Foxp3+ regulatory populations is associated with increased immunosuppression within tumors.