The Impact of Radiation Therapy on Innate and Adaptive Tumor Immunity

Abstract

The role of radiation therapy for cancer is evolving as its biologic effects on tumors becomes more clearly defined. Traditionally, radiobiology models dose-response curves based on direct cytocidal effects of radiation on tumor cells. However, a more dynamic picture is emerging of the impact of radiation on the tumor microenvironment and the patient's innate and adaptive immune system. Radiation produces damage associated molecular patterns that activate innate immune receptors leading to a cascade of downstream signals. These signals alter the tumor infiltrating immune population, modulate immune cell activation status, and enhance antigen presentation. The changes are conducive to an adaptive immune response with the generation of antitumor T cells. Early findings from clinical trials incorporating radiation and immune checkpoint inhibitors show promising synergy between the 2 modalities. As more data matures from ongoing trials, clinicians can refine new strategies for using radiation together with immunotherapy to achieve improved clinical outcomes.