Table_1_Inflammasome Deletion Promotes Anti-tumor NK Cell Function in an IL-1/IL-18 Independent Way in Murine Invasive Breast Cancer.pdf

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.

炎性体（inflammasome）是一类可在检测到病原体或危险信号时触发炎症应答的分子复合物。近年研究表明，其亦参与肿瘤进展过程。然而，炎性体在肿瘤发生过程中的具体作用仍不甚明晰且颇具争议。本研究旨在探讨炎性体激活是否可促进乳腺肿瘤生长。本研究采用侵袭性乳腺癌小鼠模型开展实验，结果显示，功能性炎性体缺失会抑制肿瘤生长。值得注意的是，移植至炎性体缺陷型小鼠体内的肿瘤，其招募的中性粒细胞数量显著减少，而自然杀伤（NK）细胞则明显增多，且后者呈现出更为活化的表型。有趣的是，耗竭NK细胞可消除炎性体缺陷型小鼠体内观察到的抗肿瘤效应，但中和炎性体调控的细胞因子却无此效果。综上，本研究揭示了炎性体通过抑制NK细胞的招募与活化，进而促进乳腺肿瘤生长的全新作用。上述研究结果提示，抑制炎性体或可成为治疗侵袭性乳腺癌的潜在靶点。