Together with pre-clinical (35, 37, 38) and clinical data (36) showing that CD155 expression on tumor cells contributes critically to resistance to anti-PD-1 immunotherapy, the pre-clinical data that demonstrate and mechanistically explain synergy between TIGIT-blockade and PD-1 blockade to enhance anti-tumor CD8+ T cell immunity, argue that dual PD-1 and TIGIT blockade is a promising combinatorial approach to overcome resistance to PD-1/PD-L1 single blockade. The gene discussed is PVR; the disease is neoplasm.