Patients with tumors in which the interferon signal transduction pathway has been inactivated by somatic mutations are refractory to PD-1 blockade therapies.81,82 In fact, apart from PD-L1 up-regulation, hyperactivated PD-L1 mutants with enhanced signal transduction capacities are selected by cancer cells to interfere with the pro-apoptotic branches of interferon signal transduction pathways.25 This evidence concerns the gene CD274 and cancer.