Inflammasome Deletion Promotes Anti-tumor NK Cell Function in an IL-1/IL-18 Independent Way in Murine Invasive Breast Cancer

Frontiers in Oncology

Thierry Walzer¹  Annabelle Drouillard¹  Anaïs Eberhardt²  Mélanie Bodnar-Wachtel²  Nathalie Bendriss-Vermare²  Christophe Caux²  Isabelle Puisieux²  Virginie Petrilli²  Baptiste Guey²  Nadège Goutagny²  Manon Pratviel² 

[1] Centre International de Recherche en Infectiologie, INSERM U1111 – CNRS UMR5308, Université de Lyon, ENS de Lyon, Université Lyon 1, Lyon, France;Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR5286, Université de Lyon, Université Lyon 1, Centre Léon Bérard, Lyon, France;

关键词: inflammasome;    breast cancer;    NK cells;    inflammation;    Caspase-1;    ASC;   

DOI  :  10.3389/fonc.2020.01683

来源: DOAJ

【 摘 要 】

Inflammasomes are molecular complexes that trigger an inflammatory response upon detection of pathogens or danger signals. Recent studies suggest that they are also involved in cancer progression. However, their roles during tumorigenesis remain poorly understood and controversial. Here, we investigated whether inflammasome activation supports mammary tumor growth. Using mouse models of invasive breast cancer, our results demonstrate that the absence of a functional inflammasome impairs tumor growth. Importantly, tumors implanted into inflammasome-deficient mice recruited significantly less neutrophils and more natural killer (NK) cells, and these latter cells displayed a more active phenotype. Interestingly, NK cell depletion abolished the anti-tumoral effect observed in inflammasome-deficient mice, although inflammasome-regulated cytokine neutralization had no effect. Thus, our work identifies a novel role for the inflammasome in supporting mammary tumor growth by attenuating NK cell recruitment and activity. These results suggest that inflammasome inhibition could be a putative target for treating invasive breast cancers.

【 授权许可】

Unknown