Immune checkpoint blockade targeting PD-1/PD-L1 has enjoyed tremendous success in the clinic against various advanced stage cancers, unleashing potent and durable immune-mediated control of tumors while vastly improving patient survival. However, only a portion of patients truly benefit, while other cancers, such as breast, prostate, pancreatic, and colon cancers, are largely resistant to PD-1/PD-L1 therapy alone. Targeting additional immunosuppressive proteins could boost the efficacy of anti-PD-1/PD-L1 therapy and bring the benefits of immunotherapy to more patients. TIGIT is a recently identified immune checkpoint protein mainly expressed by T and NK cells. CD155 (PVR) is a high-affinity receptor of TIGIT, while CD112 and CD113 bind it with weaker affinity.