Studies have demonstrated that expanded exhausted CD8+ T cells reactive to anti-PD-1/PD-L1 therapy in vivo retain high PD-1 expression (25); PD-1/PD-L1 blockade was shown to enhance IFN-γ and PD-L1 expression (42, 72) and increase tumor-infiltrating PD-1+ T cell frequencies (14). This evidence concerns the gene PDCD1 and neoplasm.