Combination of Radiotherapy and Immunotherapy in Duality with the Protumoral Action of Radiation

Radiotherapy is widely used to treat various cancers. Its combination with immune checkpoint inhibitors is intensively studied preclinically and clinically. Although the first results were very encouraging, the number of patients who respond positively remains low, and the therapeutic benefit is often temporary. This review summarizes how radiation can stimulate an antitumor immune response and its combination with immunotherapy based on inhibiting immune checkpoints. We will provide an overview of radiotherapy parameters that should be better controlled to avoid downregulating the antitumor immune response. The low response rate of combining radiotherapy and immunotherapy could, at least in part, be caused by the stimulation of cancer cell invasion and metastasis development that occur at similar doses and number of radiation fractions. To end on a positive note, we explore how a targeted inhibition of the inflammatory cytokines induced by radiation with a cyclooxygenase-2 inhibitor could both support an antitumor immune response and block radiation-induced metastasis formation.