炎症小体主要负责 IL-1β 的激活，已成为肿瘤微环境的关键调节因子。通过使用体内和体外脑转移模型以及人体样本来研究NLRP3炎症小体在三阴性乳腺癌（TNBC）脑转移中的作用，我们发现NLRP3炎症小体成分和IL-1β具有高度特异性在瘤周星形胶质细胞中表达。 TNBC 细胞的可溶性因子诱导星形胶质细胞中 NLRP3 和 IL-1β 的上调和激活，而星形胶质细胞衍生的介质则增强了转移细胞的增殖。此外，使用 MCC950 抑制 NLRP3 炎性体活性或抑制 IL-1β 的下游效应可防止癌细胞增殖增加。在体内，MCC950 降低瘤周星形胶质细胞中 IL-1β 的表达，以及炎性体成分和活性 IL-1β 的水平。最重要的是，在接受 MCC950 治疗的小鼠中观察到脑转移瘤的生长显着延缓。总体而言，星形胶质细胞通过激活 NLRP3 炎性体和随后的 IL-1β 释放，促进大脑中 TNBC 的进展。我们的结论是，炎症小体的药理学靶向可能成为控制脑转移性疾病的一种新策略。© 2023。BioMed Central Ltd.，Springer Nature 旗下公司。

Inflammasomes, primarily responsible for the activation of IL-1β, have emerged as critical regulators of the tumor microenvironment. By using in vivo and in vitro brain metastasis models, as well as human samples to study the role of the NLRP3 inflammasome in triple-negative breast cancer (TNBC) brain metastases, we found NLRP3 inflammasome components and IL-1β to be highly and specifically expressed in peritumoral astrocytes. Soluble factors from TNBC cells induced upregulation and activation of NLRP3 and IL-1β in astrocytes, while astrocyte-derived mediators augmented the proliferation of metastatic cells. In addition, inhibition of NLRP3 inflammasome activity using MCC950 or dampening the downstream effect of IL-1β prevented the proliferation increase in cancer cells. In vivo, MCC950 reduced IL-1β expression in peritumoral astrocytes, as well as the levels of inflammasome components and active IL-1β. Most importantly, significantly retarded growth of brain metastatic tumors was observed in mice treated with MCC950. Overall, astrocytes contribute to TNBC progression in the brain through activation of the NLRP3 inflammasome and consequent IL-1β release. We conclude that pharmacological targeting of inflammasomes may become a novel strategy in controlling brain metastatic diseases.© 2023. BioMed Central Ltd., part of Springer Nature.