During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called 'out-of-field' or 'abscopal' effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients.
Keywords: CTLA4; DC, dendritic cell; EBRT, external-beam radiation therapy; EGFR, epidermal growth factor receptor; FDA, Food and Drug Administration; ICD, immunogenic cell death; IL, interleukin; NHL, non-Hodgkin's lymphoma; TLR, Toll-like receptor; Toll-like receptor agonists; dendritic cells; ibritumomab tiuxetan; immunostimulatory cytokines; mAb, monoclonal antibody; peptide-based anticancer vaccine.