The immunology of ablative radiation

Radiation has been a staple of cancer therapy since the early 20th century and is implemented in nearly half of current cancer treatment plans. Originally, the genotoxic function of radiation led to a focus on damage and repair pathways associated with deoxyribonucleic acid as important therapeutic targets to augment radiation efficacy. However, in recent decades, the participation of endogenous immune responses in modifying radiation effects have been widely documented and exploited in both preclinical and clinical settings. In particular, preclinical studies have highlighted the capacity of hypofractionated-radiation dose schedules to modify endogenous immune responses raising interest in the use of hypofractionation in the clinical setting to harness the indirect immune effects of radiation and improve clinical responses. We review the current literature regarding the immunomodulatory effects of hypofractionated "ablative" radiation with a primary focus on the preclinical literature but also highlight examples from the clinical literature.