Repurposing Radiation Therapy for Immuno-oncology

Radiation therapy is traditionally used for the local control of tumour growth, but recent studies suggest that radiation therapy can have immunomodulatory properties that can be applied in combination therapy with immunotherapeutic agents. The paradigm of using radiation therapy for immunomodulation in cancer treatment is a rapidly progressing field, with multiple ongoing clinical trials exploring its use in combination with immune checkpoint blockades to induce an abscopal effect. Permutations of radiation therapy regimens, including variations in radiation dosing, radiation planning parameters and radiation modality, are being tested with varying degrees of success. The relative biological effectiveness was a concept introduced in the early days of radiation biology that allows the comparison of local tumour control across various radiation modalities and energies. Similarly, there remains a need for a new concept of comparing the immunological effectiveness of various radiation modalities. In this review, we will provide an overview of immunobiological models for preclinical and clinical monitoring of radiation therapy regimens and introduce the concept of relative immunological effectiveness to compare and screen for immune-activating functions of these regimens.