T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor that is expressed by activated T cells, Tregs, and NK cells and binds the adhesion molecules CD155 (Necl-5, also known as PVR) and CD112 (nectin-2, also known as PRR2 or PVRL2) with high and low affinity, respectively. CD155 and CD112 also bind to other ligands including the costimulatory counterpart to TIGIT, CD226 (DNAM-1), which associates with LFA-1 to positively regulate T cell responses, and CD96 (20). CD155 and CD112 play a role in T cell– and NK cell–mediated cytotoxicity against cancers. CD155 is expressed by neural tissues, endothelial cells, epithelial cells, platelets, CD14+ cells, and DCs, as well as by activated T cells and TLR-activated B cells. CD112 is expressed by endothelial cells, hematopoietic cells, and immune cells including activated T cells and B cells, CD14+ cells, and DCs. Notably, CD155 and CD112 are also expressed by various human tumors, including melanoma. Initial studies suggested that TIGIT exerts its immunosuppressive effects by enhancing IL-10 production by DCs through CD155, impeding CD4+ T cell proliferation and function. However, it was later demonstrated that TIGIT also exerts CD4+ T cell–intrinsic inhibitory effects via recruitment of SHP phosphatases that suppress cytokine production and proliferation and competes with CD226 for PVR binding. The TIGIT locus is demethylated in Tregs and may potentially bind to FOXP3. TIGIT+ Tregs are highly activated, secrete the soluble effector molecule fibrinogen-like protein 2, and selectively inhibit Th1 and Th17 responses. Most recently, TIGIT expression by CD8+ tumor-infiltrating lymphocytes (TILs) has been reported using gene expression analyses in a number of mouse and human solid cancers including lung cancer, colon cancer, breast cancer, uterine cancer, and renal cancer.
Drug targets for cancer: TIGIT research reagents
Other vital drug targets for cancer likeTIGIT:
Chauvin J-M, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients. The Journal of Clinical Investigation. 2015;125(5):2046-2058.