Cervical carcinoma induces NLRP3 inflammasome activation and IL-1ß release in human peripheral blood monocytes affecting patients' overall survival

Clin Transl Oncol. 2023 Nov;25(11):3277-3286. doi: 10.1007/s12094-023-03241-2. Epub 2023 Jun 16.

Abstract

Purpose: Our group previously demonstrated that genetic variants in inflammasome genes contribute to protection against the establishment of human papilloma virus (HPV)-associated cervical carcinoma (CC). The objective of this study was to better understand the contribution of inflammasome and its cytokines in the CC microenvironment.

Methods: The inflammasome activation was analyzed in CC tumoral cell lines and healthy donors (HD)' monocytes in co-culture. In vitro results were then compared to CC patients' public databases.

Results: CC cells did not produce IL-1ß or IL-18 themselves, however, when in co-culture with HD monocytes, induced IL-1ß release in those leucocytes. Inflammasome activation appears to be partially dependent on the NLRP3 receptor. Public data analysis revealed that IL1B expression is increased in the CC compared to normal uterine cervix, and that patients with high IL1B expression had a shorter overall survival.

Conclusion: CC microenvironment can activate the inflammasome and IL-1ß release in surrounding monocytes, which could be detrimental for CC prognosis.

Keywords: Cervical cancer; IL-1ß; Inflammasome; NLRP3.

MeSH terms

  • Carcinoma* / metabolism
  • Female
  • Humans
  • Inflammasomes / genetics
  • Inflammasomes / metabolism
  • Monocytes / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Tumor Microenvironment
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein