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

Signal Transduction and Targeted Therapy

Article

Xikun Zhou¹  Teng Ma¹  Yige Zhang¹  Yu Tang¹  Yongxin Zhang¹  Yang Yang¹  Xueli Hu¹  Qianhua Zhang¹  Ruihuan Wang¹  Huan Liu¹  Taolin Wang¹  Mingbo Wu¹  Miao Tang¹  Chaoyu Zou¹  Heyue Li¹  Yuan Ren²  Yi Li³  Min Wu⁴  Jing Li⁵ 

[1] Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China;Department of Breast Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 610072, Chengdu, China;Drug Discovery Center, Wenzhou Institute, University of Chinese Academy of Sciences, 325001, Wenzhou, China;State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China;

关键词: ;   

DOI  :  10.1038/s41392-023-01542-0

 received in 2023-02-03, accepted in 2023-06-14,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© West China Hospital, Sichuan University 2023

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