Radiation therapy and the abscopal effect: a concept comes of age

The concept of utilizing localized radiation therapy to elicit out-of-target tumor responses—the abscopal effect—was proposed over 50 years ago (1,2). Over the past decades, the abscopal mechanism has been elucidated by the work of many investigators, including Formenti and Demaria, who showed that this process was likely mediated by the immune system leading to immunogenic tumor cell death, a process which involves dendritic cells, T regulatory cells, and suppressor cells as critical mediators (3-5). This research was inspired by the hypothesis that targeted radiotherapy in the proper setting can produce a consistent and robust abscopal effect, thus delivering clinically meaningful anti-tumor responses and disease control, if not eradicating distal disease in patients with metastatic cancer. The recent successes of several immune check point inhibitor clinical trials in various malignancies have demonstrated wide applicability and enormous therapeutic potential of immunomodulation and have galvanized keen interest in this field (6-10). An ambitious goal of combining radiotherapy and immunotherapy in the clinic would be long term remission for cancer patients with metastatic disease, perhaps through an approach analogous to delivering an in-situ anti-tumor vaccine (11-13).