Grassberger et al. review biomarkers, imaging techniques, and models used to evaluate the immune response to tumor radiotherapy. Serum biomarkers such as circulating immune cells, cytokines, and antibodies are highlighted for their noninvasive, systemic readout. MRI, SPECT, and PET can image the immune response, labeling cells either ex vivo for re-infusion and tracking or in vivo. Recent mathematical models treat the tumor either as single or multiple compartments, considering heterogeneity and dynamics between metastatic sites. In the future, these methods may inform optimal dose, timing, fractionation, and site of radiotherapy in cancer.
Contributed by Alex Najibi
Immunotherapy, specifically the introduction of immune checkpoint inhibitors, has transformed the treatment of cancer, enabling long-term tumour control even in individuals with advanced-stage disease. Unfortunately, only a small subset of patients show a response to currently available immunotherapies. Despite a growing consensus that combining immune checkpoint inhibitors with radiotherapy can increase response rates, this approach might be limited by the development of persistent radiation-induced immunosuppression. The ultimate goal of combining immunotherapy with radiotherapy is to induce a shift from an ineffective, pre-existing immune response to a long-lasting, therapy-induced immune response at all sites of disease. To achieve this goal and enable the adaptation and monitoring of individualized treatment approaches, assessment of the dynamic changes in the immune system at the patient level is essential. In this Review, we summarize the available clinical data, including forthcoming methods to assess the immune response to radiotherapy at the patient level, ranging from serum biomarkers to imaging techniques that enable investigation of immune cell dynamics in patients. Furthermore, we discuss modelling approaches that have been developed to predict the interaction of immunotherapy with radiotherapy, and highlight how they could be combined with biomarkers of antitumour immunity to optimize radiotherapy regimens and maximize their synergy with immunotherapy.