- TIGIT is an immune checkpoint receptor on cytotoxic, memory, and Tregs, as well as NK
- On cytotoxic T cells and NK cells, interaction of TIGIT with either of its 2 ligands, CD155 (PVR) and CD112 (Nectin2), suppresses immune activation1,2
- When TIGIT is expressed on Tregs, however, this interaction enhances their ability to suppress the immune response3
- The suppressive effect of TIGIT is counterbalanced by the
immune-activatingreceptor CD226 (also called DNAM1), which is also expressed on cytotoxic T cells and NK cells and competes with TIGIT to bind to CD155 and CD1124,5
- The inhibitory signal provided by TIGIT overpowers DNAM1’s ability to stimulate T-cell activation5
- In cancer, tumor cells exploit the inhibitory TIGIT pathway to avoid immune-mediated destruction
1. Yu X, Harden K, Gonzalez LC, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48-57. 2. Stanietsky N, Simic H, Arapovic J, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A. 2009;106(42):17858-17863. 3. Joller N, Lozano E, Burkett PR, et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity. 2014;40(4):569-581. 4. Bottino C, Castriconi R, Pende D, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med.