Mini-review of Conventional and Hypofractionated Radiation Therapy Combined with Immunotherapy for Non-small Cell Lung Cancer

A successful antitumoral response requires immunological activation as well as an antigenic pool capable of stimulating both the innate and the adaptive immune system. Recent advances in immunotherapy have been aimed at boosting the activation status of the innate and adaptive immune system, including cytokine administration, monoclonal antibodies engineered to target high yield elements in oncogenic signaling pathways, cancer vaccines, and checkpoint inhibitors. Herein, we examine the ways that radiation therapy induced cell death provides a pool of stimulus antigen, and draw parallels from the immunobiology of autoimmunity to explore how the immunogenicity of antigen derived from radiation-induced cell death might augment the antitumoral response. We also review basic research into the ability of different radiation dose fractionation schedules to induce an antitumoral response. After a discussion of basic immunotherapeutic principles, we review the published literature in the field of non-small cell lung cancer (NSCLC) and examine the ways that combining radiation and immunotherapy have begun to change the therapeutic terrain. We provide a summary of ongoing clinical trials aimed at combining immunotherapy and radiation therapy in NSCLC while emphasizing the need for identification of biomarkers with predictive power and the assessment of efficacy as a function of fractionation strategy.