High versus low dose irradiation for tumor immune reprogramming

Local administration of ionizing radiation to tumors can promote anticancer immune responses that lead to the abscopal regression of distant metastases, especially in patients receiving systemic immune-checkpoint inhibitors. Growing preclinical evidence indicates that high-dose irradiation administered locally to destroy malignant lesions, can promote the release of danger-associated molecular patterns that lead to the recruitment of immune cells, thus inducing a systemic response against tumor antigens that protects against local disease relapse and also mediates distant antineoplastic effects. An accumulating body of preclinical evidence supports also the implementation of low-dose irradiation to induce tumor immune reprogramming. Here, we provide the rationale for a clinical research agenda to refine future clinical practice based on innovative combinations of radiation-immunotherapy.