PDCD1 and neoplasm: Resistance to anti-PD-1/PD-L1 therapy may arise from intrinsic tumor factors, such as PTEN loss, β-catenin signaling, and VEGF-mediated immune exclusion, as well as from adaptive feedback, in which inflammatory cytokines, like IFN-γ, up-regulate PD-L1, thereby reinforcing immunosuppression (129).