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

Nat Immunol. 2020 Feb;21(2):120-134. doi: 10.1038/s41590-019-0561-4. Epub 2019 Dec 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death / radiation effects*
  • Humans
  • Signal Transduction / immunology*
  • Signal Transduction / radiation effects*
  • Tumor Microenvironment / immunology*
  • Tumor Microenvironment / radiation effects*