The optimism surrounding stereotactic body radiation therapy and immunomodulation.

In recent years, rapidly evolving radiation techniques have enabled the precise delivery of very high doses of radiation to local targets with stereotactic ablative body radiotherapy (SABR). In addition to its direct cytotoxicity, radiation and in particular SABR has powerful immunomodulatory effects resulting in immunogenic cell death and potentiation of the anti-tumour immune response. However, due to the immunosuppressive nature of non-irradiated sites of metastases, radiotherapy alone is seldom sufficient to induce the systemic response required for distant tumour rejection. Immune checkpoint inhibitors are a novel class of immunomodulatory agents shown to have robust efficacy against a number of malignancies. These drugs can augment the effects of radiotherapy by helping overcome tumour-induced immunosuppression at local and distant sites. Similarly, radiation may complement immunotherapy by priming tumours in preparation for the adaptive immune response, thereby leading to more prolonged clinical effects. This synergistic relationship has been demonstrated in laboratory models and has been extended to a number of early phase clinical studies.