Immune recognition of irradiated cancer cells

Erik Wennerberg, Claire Vanpouille-Box, Sophia Bornstein, Takahiro Yamazaki, Sandra Demaria, Lorenzo Galluzzi

Research output: Contribution to journalReview articlepeer-review

60 Scopus citations


Ionizing irradiation has been extensively employed for the clinical management of solid tumors, with therapeutic or palliative intents, for decades. Until recently, radiation therapy (RT) was believed to mediate antineoplastic activity mostly (if not only) as a consequence of cancer cell-intrinsic effects. Indeed, the macromolecular damage imposed to malignant cells by RT initiates one or multiple signal transduction cascades that drive a permanent proliferative arrest (cellular senescence) or regulated cell death. Both these phenomena show a rather linear dose-response correlation. However, RT also mediates consistent immunological activity, not only as an “on-target effect” originating within irradiated cancer cells, but also as an “off-target effect” depending on the interaction between RT and stromal, endothelial, and immune components of the tumor microenvironment. Interestingly, the immunological activity of RT does not exhibit linear dose-response correlation. Here, we discuss the mechanisms whereby RT alters the capacity of the immune system to recognize and eliminate irradiated cancer cells, either as an “on-target” or as on “off-target” effect. In particular, we discuss the antagonism between the immunostimulatory and immunosuppressive effects of RT as we delineate combinatorial strategies to boost the former at the expenses of the latter.

Original languageEnglish (US)
Pages (from-to)220-230
Number of pages11
JournalImmunological reviews
Issue number1
StatePublished - Nov 2017


  • NKG2D
  • autophagy
  • danger signaling
  • immunogenic cell death
  • mutational load
  • tumor neoantigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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