Preclinical studies of combined DNA-PK inhibition, radiation and PD-L1 blockade demonstrated increased anti-tumor activity in a p53-mutant cancer, suggesting that inhibition of DNA-PK inhibits repair of radiation-induced DSBs resulting in potentiation of anti-tumor immunity, adaptive PD-L1 expression through DDR-dependent mechanisms, and subsequent responsiveness to immune checkpoint blockade (132). The gene discussed is PRKDC; the disease is cancer.