Figure 1.

Primary and secondary effects of radiation. The primary target of radiation within the tumor cells is the DNA. It aims to eliminate the tumor through inhibition of its proliferating capacity and by induction of cell death. Necrosis, apoptosis, mitotic catastrophe (MC), autophagy, and senescence might occur after radiation-induced DNA-damage. However, radiotherapy (RT) also has a secondary, non-targeted effect that is achieved through a modification of the tumor phenotype, the tumor microenvironment, and/or the induction of an immunogenic cell death (ICD), characterized by the release of danger-associated molecular patterns (DAMPs) and cytokines (e.g., but not exclusively Hsp70, HMGB1, IL-6, IL-8; TNF-α). All of these contribute to the activation of immune-mediated local and distant reactions on the tumor and metastases.