The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation

Chuanhui Han, Victoria Godfrey, Zhida Liu, Yanfei Han, Longchao Liu, Hua Peng, Ralph R. Weichselbaum, Hasan Zaki, Yang Xin Fu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The inflammasome promotes inflammation-associated diseases, including cancer, and contributes to the radiation-induced tissue damage. However, the role of inflammasome in radiation-induced antitumor effects is unclear. We observed that tumors transplanted in Casp1-/- mice were resistant to radiation treatment compared with tumors in wild-type (WT) mice. To map out which molecule in the inflammasome pathway contributed to this resistant, we investigated the antitumor effect of radiation in several inflammasome-deficient mice. Tumors grown in either Aim2-/- or Nlrp3-/- mice remained sensitive to radiation, like WT mice, whereas Aim2-/-Nlrp3-/- mice showed radioresistance. Mechanistically, extracellular vesicles (EVs) and EV-free supernatant derived from irradiated tumors activated both Aim2 and Nlrp3 inflammasomes in macrophages, leading to the production of interleukin-1β (IL-1β). IL-1β treatment helped overcome the radioresistance of tumors growing in Casp1-/- and Aim2-/-Nlrp3-/- mice. IL-1 signaling in dendritic cells (DCs) promoted radiation-induced antitumor immunity by enhancing the cross-priming activity of DCs. Overall, we demonstrated that radiation-induced activation of the AIM2 and NLRP3 inflammasomes coordinate to induce some of the antitumor effects of radiation by triggering IL-1 signaling in DCs, leading to their activation and cross-priming.

Original languageEnglish (US)
Article numbereabc6998
JournalScience Immunology
Volume6
Issue number59
DOIs
StatePublished - May 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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