Immunological impact of cell death signaling driven by radiation on the tumor microenvironment

• Published in: Nature immunology Vol. 21; no. 2; pp. 120 - 134
• Main Authors: Rodriguez-Ruiz, Maria Esperanza, Vitale, Ilio, Harrington, Kevin J., Melero, Ignacio, Galluzzi, Lorenzo
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2020; Nature Publishing Group
• Subjects: 631/250/580; 631/67/580; 631/80/509; 631/80/82; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer; Cell death; Cell Death - radiation effects; Cytokines; Cytotoxicity; Health aspects; Humans; Immune response; Immunology; Immunomodulation; Infectious Diseases; Irradiation; Radiation; Radiation therapy; Review Article; Signal Transduction - immunology; Signal Transduction - radiation effects; Tumor microenvironment; Tumor Microenvironment - immunology; Tumor Microenvironment - radiation effects; Spain
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/s41590-019-0561-4

Therapeutic irradiation of the tumor microenvironment causes differential activation of pro-survival and pro-death pathways in malignant, stromal, endothelial and immune cells, hence causing a profound cellular and biological reconfiguration via multiple, non-redundant mechanisms. Such mechanisms include the selective elimination of particularly radiosensitive cell types and consequent loss of specific cellular functions, the local release of cytokines and danger signals by dying radiosensitive cells, and altered cytokine secretion by surviving radioresistant cells. Altogether, these processes create chemotactic and immunomodulatory cues for incoming and resident immune cells. Here we discuss how cytoprotective and cytotoxic signaling modules activated by radiation in specific cell populations reshape the immunological tumor microenvironment. Radiation therapy has for decades been a standard form of treatment for many cancers. A Review by Galluzzi and colleagues explores the effects of radiation therapy in the context of the immune response.