T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), an immune checkpoint receptor, can suppress T-cell activation and promote T-cell exhaustion. Inhibition of TIGIT may increase cytotoxic T-cell proliferation and function.
TIGIT is an immune checkpoint receptor on cytotoxic, memory, and Tregs, as well as NK cells.1,2
On cytotoxic T cells and NK cells, interaction of TIGIT with either of its 2 ligands, CD155 (PVR) and CD112 (Nectin2), suppresses immune activation.1,2
When TIGIT is expressed on Tregs, however, this interaction enhances their ability to suppress the immune response.3
The suppressive effect of TIGIT is counterbalanced by the immune-activating receptor CD226 (also called DNAM1), which is also expressed on cytotoxic T cells and NK cells and competes with TIGIT to bind to CD155 and CD112.4,5
The inhibitory signal provided by TIGIT overpowers DNAM1’s ability to stimulate T-cell activation.5
In cancer, tumor cells exploit the inhibitory TIGIT pathway to avoid immune-mediated destruction.