Exploring optimal sequencing of radiation and immunotherapy combinations

PURPOSE: The purpose of this article is to assemble, review, and provide a synopsis of the historical and current literature regarding optimal sequencing of radiation (RT) and immunotherapy combination treatments. MATERIALS AND METHODS: A review of the literature was performed using PubMed with the query “radiation” and “Immunotherapy”, “PD1”, “PDL1”, “CTLA4”, “OX40”, “checkpoint”, “vaccine”, “macrophage”, “STING”, and “TGFbeta”. Studies that included sequencing of therapy were evaluated and the studies were included at the authors discretion. RESULTS: A paucity of primary literature exists examining the best order of radiation and immunotherapy, most of which was performed in the pre-clinical setting. The observations are that optimal sequencing of various radiation plus immune therapy combinations is dependent on the mechanism(s) of activation by the combination treatment. Immunosuppressive molecules tend to be better inhibited prior to RT while engagement of costimulatory genes is better activated concomitantly with RT. CONCLUSIONS: These data should compel more basic research into both the direct investigation of sequencing efficacy and studies on the mechanisms of immune mediated cell death potentiated by radio-therapy.