PD-L1 undoubtedly inhibits T cell effector activities by binding PD-1.5,83,84,86,92 However, it is becoming evident that PD-L1 directly favors cancer cell survival and tumor progression via the modulation of metabolic pathways.88,90,93 The therapeutic activities of PD-L1/PD-1-blocking antibodies can be ascribed to two simultaneous mechanisms—reactivation of tumor-infiltrating T cells that would then produce cytotoxic mediators, such as IFNs, and sensitization of cancer cells to IFN-induced apoptosis25—directly potentiating cytotoxicity over cancer cells. This evidence concerns the gene CD274 and cancer.