Damage-associated molecular patterns in tumor radiotherapy

Radiotherapy is one of the most common modalities for the treatment of cancer. One of the most promising effects of radiotherapy is immunologic cell death and the release of danger alarms, which are known as damage-associated molecular patterns (DAMPs). DAMPs are able to trigger cancer cells and other cells within tumor microenvironment (TME), either for suppression or promotion of tumor growth. Heat shock proteins (HSPs) including HSP70 and HSP90, high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) and its metabolites such as adenosine are the most common danger alarms that are released after radiotherapy-induced immunologic cell death. Some DAMPs including adenosine is able to interact with both cancer cells as well as other cells in TME to promote tumor growth and resistance to radiotherapy. However, others are able to trigger anti-tumor immunity or both tumor suppressive and immunosuppressive mechanisms depending on affected cells. In this review, we explain the mechanisms behind the release of radiation-induced DAMPs, and its consequences on cells within tumor. Targeting of these mechanisms may be in favor of tumor control in combination with radiotherapy and radioimmunotherapy.