Immune System Activation in Patients with Metastatic Renal Cell Carcinoma Induced by the Systemic Abscopal Effects of Radiation Therapy

Introduction: Renal cell carcinoma (RCC) is characterized by large histopathologic heterogeneity and classified with multiple histological subtypes. Radiation therapy has long played a key role in the management of both local and metastatic RCC. An out-of-field tumor regression (abscopal response) effect of radiation therapy has gained significant importance in the treatment of different tumor types including RCC. In this study, we provide a detailed overview of the current state of knowledge and clinical experience of radiation therapy-induced abscopal effects in patients with advanced RCC. Methods: The PRISMA guidelines were followed to identify the published articles for the study. Using electronic databases such as MEDLINE via PubMed and Google Scholar, a systematic literature review was performed to find published clinical evidence for radiation therapy-induced abscopal effects in patients with advanced RCC. The clinical data of radiation therapy-induced abscopal effects were reviewed, and the outcomes have been summarized. Results: In this study, we evaluated peer-reviewed published reports to find clinical evidence for the abscopal effect following radiation therapy in patients with advanced RCC. The clinical data on the systemic abscopal effects of radiation therapy were reviewed, and the outcomes were summarized. Our literature search indicated that the evidence for abscopal effects of radiation therapy in advanced RCC yielded over 20 case reports. The evidence indicates that abscopal effects of local radiation therapy may occur in RCC through tumor cell destruction with the subsequent release of tumor antigens that systemically stimulate the immune system of the host to activate the body’s immune effector cells and produce distant nontarget antitumor effects. The activation of the immune system by local radiation therapy forms the basis to combine immunotherapy to boost its abscopal effects. Conclusions: Collectively, these findings suggest that radiation therapy can induce systemic abscopal effects through immune system activation, and thus, the addition of immunotherapeutic agents increases the potential to boost the systemic abscopal responses in patients with advanced cancers including RCC.