Understanding the Effects of Radiotherapy on the Tumour Immune Microenvironment to Identify Potential Prognostic and Predictive Biomarkers of Radiotherapy Response

SIMPLE SUMMARY: Around 50% of all cancer patients receive radiotherapy as part of their treatment. Recently immunotherapy has shown promising results and become established as an effective treatment for some cancers. Combining radiotherapy and immunotherapy is a novel approach to further increase the number of patients responding to immunotherapy. Biological markers of response (biomarkers) are urgently required to hasten the clinical translation and improve outcomes further. Radiotherapy can both stimulate and inhibit the immune system and understanding the immune effects of radiotherapy on the tumour and surrounding cells may lead to the identification of predictive and prognostic biomarkers to help make more individualized treatment decisions, when combining radiotherapy with immunotherapy. This review summarizes the immune effects of radiotherapy and biomarkers of response identified to date; providing new perspectives for future research which may facilitate the development of novel radiotherapy immunotherapy combinations based on tumour immunology and biomarker identification. ABSTRACT: Radiotherapy (RT) is a highly effective anti-cancer treatment. Immunotherapy using immune checkpoint blockade (ICI) has emerged as a new and robust pillar in cancer therapy; however, the response rate to single agent ICI is low whilst toxicity remains. Radiotherapy has been shown to have local and systemic immunomodulatory effects. Therefore, combining RT and immunotherapy is a rational approach to enhance anti-tumour immune responses. However, the immunomodulatory effects of RT can be both immunostimulatory or immunosuppressive and may be different across different tumour types and patients. Therefore, there is an urgent medical need to establish biomarkers to guide clinical decision making in predicting responses or in patient selection for RT-based combination treatments. In this review, we summarize the immunological effects of RT on the tumour microenvironment and emerging biomarkers to help better understand the implications of these immunological changes, and we provide new insights into the potential for combination therapies with RT and immunotherapy.