Cancer Immunology at the Crossroads: Complementary Therapeutic Modalities Harnessing the Potential of Radiation-Induced Immune Modulation for Cancer Therapy

The conventional use of radiotherapy is for local tumor control. Radiotherapy of the primary tumor can prevent the development of distant metastases, but this modality is generally not effective for treating preexisting systemic disease. However, radiation-induced tumor destruction may be considered a novel strategy for in situ cancer vaccination, in which tumor antigens released from dying tumor cells may be presented in an immunostimulatory context. Moreover, radiation has been demonstrated to induce immunogenic modulation in various tumor types by altering the biology of surviving cells to render them more susceptible to T cell– mediated killing. Finally, radiotherapy typically has a favorable toxicity profile and is associated with the absence of systemic immunosuppression. Together, these properties suggest that radiotherapymay serve as an important component of combinatorial immunotherapies aimed at augmenting systemic antitumor immunity. Here, we provide an overview of the radiation-induced modulations of the immune system that may be harnessed for cancer therapy. Cancer Immunol Res; 1(5); 280–4. 2013 AACR