Abstract
PURPOSE OF REVIEW: This review aims to summarize the current preclinical and clinical evidence of nontargeted immune effects of spatially fractionated radiation therapy (SFRT). We then highlight strategies to augment the immunomodulatory potential of SFRT in combination with immunotherapy (IT). RECENT FINDINGS: The response of cancer to IT is limited by primary and acquired immune resistance, and strategies are needed to prime the immune system to increase the efficacy of IT. Radiation therapy can induce immunologic effects and can potentially be used to synergize the effects of IT, although the optimal combination of radiation and IT is largely unknown. SFRT is a novel radiation technique that limits ablative doses to tumor subvolumes, and this highly heterogeneous dose deposition may increase the immune-rich infiltrate within the targeted tumor with enhanced antigen presentation and activated T cells in nonirradiated tumors. The understanding of nontargeted effects of SFRT can contribute to future translational strategies to combine SFRT and IT. Integration of SFRT and IT is an innovative approach to address immune resistance to IT with the overall goal of improving the therapeutic ratio of radiation therapy and increasing the efficacy of IT.