Fig. 2
From: Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials
Mechanism of co-inhibition by TIGIT and PD-1. The TIGIT/CD226 pathway and the PD-1/PD-L1 pathway have an intersecting crossroad. On the one hand, upon activation by PD-L1, the intracellular domain of PD-1 recruits Shp2 to dephosphorylate CD226, inhibiting the immune activation function of CD226. On the other hand, TIGIT has a higher affinity (dissociation constant 1–3 nM) to CD155 than that of CD226 (dissociation constant 119 nM) [25], thus competitively antagonizes and blocks CD226 homodimerization through its extracellular domain, inhibiting the immune activation function of CD226.