The synergistic effect of radiotherapy and immunotherapy: A promising but not simple partnership

- The combination of radiotherapy (RT) and immunotherapy are under active investigation.
- We propose an overview of the molecular bases of the immune activation induced by RT.
- The clinical applications and the RT specificities to be considered when combining RT with immunotherapy are discussed.

Radiotherapy (RT) is one of the main components in the treatment of cancer. The better understanding of the immune mechanisms associated with tumor establishment and how RT affects inflammation and immunity has led to the development of novel treatment strategies. Several preclinical studies support the use of RT in combination with immunotherapy obtaining better local and systemic tumor control. Current ongoing studies will provide information about the optimal RT approach, but the development of reliable predictors of the response from the preclinical and the early phases of clinical studies is necessary to avoid discarding treatment strategies with significant clinical benefit. This review summarize the current concepts of the synergism between RT and immunotherapy, the molecular effects of RT in the tumor microenvironment, their impact on immune activation and its potential clinical applications in trials exploring this important therapeutic opportunity. Finally, the potential predictors of clinical response are discussed.