Radiotherapy and Immunogenic Cell Death

Advances in understanding the mechanisms that underlie the interplay between radiation-invoked immune responses and tumor regression are underway. Emerging applications of local radiotherapy as an immunologic adjuvant have provided radiation oncologists with a method for converting malignant cells into endogenous anticancer vaccines. The dispersion of radiotherapy-induced immune-stimulating tumor antigens released from dying tumor cells into the surrounding milieu (known as immunogenic cell death, Fig. 1), is one such exploitable process that contributes to the propagation of antitumor immunity. Downstream components of the immune system may suppress, promote, or ambiguously affect antitumoral responses. Additionally, host, tumor, and treatment-related characteristics govern the significance of these signals, thereby dictating therapeutic outcomes. Herein, we review the process of radiotherapy-induced immunogenic cell death and its role in generating an in situ vaccine to help refine radioimmunotherapy-based protocols.