Abstract IA-013: Integrating radiation therapy with immunotherapy

Abstract

Abstract We have shown that when studied in isolation, radiation therapy functions poorly as an endogenous vaccine, and that many of the promising therapeutic approaches of radiation in combination with immunotherapy depends on a pre-existing immune response. Therefore, focusing primarily on radiation as an in situ vaccine strategy may yield limited results. We have identified that the ability of radiation therapy to function as a vaccine is dependent on its ability to activate the cDC1 subpopulation of dendritic cells in the tumor and that a lack of endogenous adjuvant and/or active suppression following radiation resulting in lack of maturation of cDC1 may be a major factor that limits control of poorly radioimmunogenic tumors. However, where radiation therapy and immunotherapy combinations work well, radiation therapy cannot be adequately replaced by a potent tumor vaccine, demonstrating that radiation therapy provides critical effects beyond priming new T cell responses. In addition to potential vaccine effects of radiation, it also modifies the cancer cells in the field to make them a better target for control by immune cells. We recently demonstrated that one of the major roles that radiation can play in controlling tumors when combined with immunotherapy is to increase the susceptibility of surviving cancer cells to CD8+ T cells through induction of MHC-I through genetic upregulation of the MHC-I transactivator NLRC5. These data support the critical role of local modulation by radiation in improved tumor control with combination immunotherapy. Citation Format: Marka Crittenden. Integrating radiation therapy with immunotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-013.