Interfaces Between the DNA Damage Response and Anti-cancer Immunity

The complex interplay between DNA damage (DDR) and immune responses presents therapeutic opportunities for enhancing antitumour immunity, particularly in the context of radiotherapy. We discuss how DNA damage leads to immunomodulation and how conventional DNA-damaging therapies modulate the immune response, with both immunostimulatory and immunosuppressive effects. We discuss present clinically exploited DDR-immune links, such as the use of genomic instability and DDR status as predictive biomarkers. We present strategies, such as combined DDR-radiation, which have shown promise in preclinical and early clinical studies as immunomodulatory radiosensitizing therapies.