Immunological Consequences of Uniform vs Spatially Fractionated Radiotherapy

Radiotherapy (RT) is the single most frequently used cancer treatment, with approximately 60% of patients undergoing either monotherapy or combination with other therapeutics. The immunogenicity of the tumor micro-environment (TME) affects how well a tumor responds to treatment. TMEs can be hot or cold, with tumors in immunologically cold micro-environments generally showing less of a radiation response than those in immunologically hot micro-environments. Radiation can be immunosuppressive or immuno-stimulatory, but these contradictory effects are poorly understood. It is thought that the immune response initiated by radiotherapy is curtailed by subsequent application of RT. Spatially fractionated radiotherapy shields areas of the tumor, thereby potentially protecting the immune environment. An ABM model was developed to evaluate the effects that different radiation doses, scheduling and SFRT architectures have on the immunological consequences of RT. We identify which types of TME respond better to spatially uniform or spatially fractionated radiotherapy, in the pursuit of advancing radiotherapy personalization.