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. 2018 May 7;19(5):1389. doi: 10.3390/ijms19051389

Figure 2.

Figure 2

Mutual regulation by the PD-1/CD226/TIGIT/CD96 pathways. TIGIT and CD96 bind to PVR with a higher affinity than CD226 and outcompete CD226 for binding to inhibit T cell activation. TIGIT triggering of PVR induces an inhibitory signal into tumor cells, which up-regulates IL-10 and down-regulates IL-12. TIGIT interferes with CD226 homodimerization in cis and prevents CD226/PVR engagement. Whether TIGIT can directly deliver co-inhibitory signals in T cells after binding to PVR remains unclear. CD226 binds to CD112 and PVR to deliver co-stimulatory signals. CD96 binds to CD111 and PVR to deliver co-inhibitory signals. PD-1 binds to PD-L1 and interferes with CD226 signal transduction to maintain immune resistance in the TME.