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

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-1 beta (IL-1 beta). IL-1 beta 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.

Automated summary

Research showed that tumors lacking certain molecules in the inflammasome pathway were sensitive to radiation treatment in mice, while dual deficiency in multiple molecules resulted in radioresistance. The study also demonstrated that activation of AIM2 and NLRP3 inflammasomes by irradiated tumors played a role in inducing antitumor effects through IL-1 signaling in dendritic cells.