Preclinical studies with hypofractionated regimens have revealed that increased doses of ionizing radiation (IR) induce potent anti-tumor immune responses, as a result of IR-induced immunogenic tumor cell death. These insights have boosted an immense level of translational and clinical research at the interface of radiotherapy and immunology leading to promising clinical trials of radiotherapy in combination with immune checkpoint inhibitors. However, we have only limited insight on such fundamental questions how radiotherapy with larger treatment volumes will affect the immune system and subsequently the tumor immune response. Here we will investigate the impact of the radiotherapy treatment volume on the efficacy and the immune response alone and in combination with immune checkpoint inhibitors against the irradiated primary tumor and abscopal tumor burdens.
This project will, using adequate preclinical murine tumor models and a state-of-the art small animal image-guided radiotherapy platform, establish a relationship between the size of the radiotherapy treatment volume directed against the primary tumor, the immunological responses and the therapeutic outcome towards the primary but also the non-irradiated secondary tumor. This research project will therefore contribute to a better understanding and potential treatment optimization of patients in this scenario.