Although the neoantigen-T cell activation-IFN-γ-STAT1/3-IRF1 pathway of PD-L1 induction has historically been viewed as the chief mediator of this adaptive immune resistance, recent work has implicated DNA damage and repair signaling in the regulation of tumor PD-L1, including through radiation-mediated DSBs and cytosolic DNA sensing. The gene discussed is CD274; the disease is neoplasm.