研究动态
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慢性肺部细菌感染通过招募促进肿瘤的MHCII高表达中性粒细胞,促使乳腺癌在肺部发生转移。

Chronic pulmonary bacterial infection facilitates breast cancer lung metastasis by recruiting tumor-promoting MHCIIhi neutrophils.

发表日期:2023 Aug 11
作者: Teng Ma, Yu Tang, Taolin Wang, Yang Yang, Yige Zhang, Ruihuan Wang, Yongxin Zhang, Yi Li, Mingbo Wu, Miao Tang, Xueli Hu, Chaoyu Zou, Yuan Ren, Huan Liu, Qianhua Zhang, Heyue Li, Min Wu, Jing Li, Xikun Zhou
来源: Signal Transduction and Targeted Therapy

摘要:

乳腺癌可转移到多个器官,包括肺部。待转移器官的免疫微环境在乳腺癌的转移过程中起着至关重要的作用。病毒和细菌等病原体感染可以改变肺部的免疫状态。然而,由细菌引起的慢性炎症对肺部早转移巢中的形成的影响尚不清楚,而特定免疫介质在肿瘤转移中的贡献也基本尚未确定。在这里,我们使用小鼠模型发现,慢性肺部细菌感染通过招募一种独特的MHCIIhi中性粒细胞亚型加剧了乳腺癌肺转移,这些细胞具有促癌性能。功能上,MHCIIhi中性粒细胞以细胞内机制增强了乳腺癌在肺部的转移。此外,我们发现肺组织中的CCL2是招募和维持MHCIIhi中性粒细胞的重要环境信号。我们的发现明确地将细菌免疫交互作用与乳腺癌肺转移联系起来,并将MHCIIhi中性粒细胞定义为慢性感染与肿瘤转移之间的主要介质。© 2023. 四川大学华西医院。
Breast cancer can metastasize to various organs, including the lungs. The immune microenvironment of the organs to be metastasized plays a crucial role in the metastasis of breast cancer. Infection with pathogens such as viruses and bacteria can alter the immune status of the lung. However, the effect of chronic inflammation caused by bacteria on the formation of a premetastatic niche within the lung is unclear, and the contribution of specific immune mediators to tumor metastasis also remains largely undetermined. Here, we used a mouse model revealing that chronic pulmonary bacterial infection augmented breast cancer lung metastasis by recruiting a distinct subtype of tumor-infiltrating MHCIIhi neutrophils into the lung, which exhibit cancer-promoting properties. Functionally, MHCIIhi neutrophils enhanced the lung metastasis of breast cancer in a cell-intrinsic manner. Furthermore, we identified CCL2 from lung tissues as an important environmental signal to recruit and maintain MHCIIhi neutrophils. Our findings clearly link bacterial-immune crosstalk to breast cancer lung metastasis and define MHCIIhi neutrophils as the principal mediator between chronic infection and tumor metastasis.© 2023. West China Hospital, Sichuan University.