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The AIM2 and NLRP3 inflammasomes trigger IL-1–mediated antitumor effects during radiation
- Source :
- Science Immunology. 6
- Publication Year :
- 2021
- Publisher :
- American Association for the Advancement of Science (AAAS), 2021.
-
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.
- Subjects :
- 0301 basic medicine
Inflammasomes
Interleukin-1beta
Immunology
Mice, Transgenic
CD8-Positive T-Lymphocytes
Radiation Tolerance
Extracellular vesicles
03 medical and health sciences
AIM2
0302 clinical medicine
Neoplasms
Radioresistance
NLR Family, Pyrin Domain-Containing 3 Protein
Tissue damage
medicine
Animals
Cells, Cultured
Mice, Inbred BALB C
Antitumor immunity
Chemistry
Macrophages
Caspase 1
Cancer
Inflammasome
Dendritic Cells
General Medicine
medicine.disease
Coculture Techniques
DNA-Binding Proteins
Mice, Inbred C57BL
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Female
medicine.drug
Subjects
Details
- ISSN :
- 24709468
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Science Immunology
- Accession number :
- edsair.doi.dedup.....3f28a76e4d5ae62985dd21fe405f04aa