Bifidobacterium adolescentis induces Decorin+ macrophages via TLR2 to suppress colorectal carcinogenesis

Journal of Experimental & Clinical Cancer Research

Research

Yadong Qi¹  Shujie Chen²  Lina Fan³  Yifeng Lin³  Dingjiacheng Jia³  Yao Jiang³  Chaochao Xu³  Liangjing Wang⁴ 

[1] Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, 310003, Hangzhou, Zhejiang Province, China;Institute of Gastroenterology, Zhejiang University, Hangzhou, China;Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, 310003, Hangzhou, Zhejiang Province, China;Institute of Gastroenterology, Zhejiang University, Hangzhou, China;Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China;Research Center of Prevention and Treatment of Senescent Disease, School of Medicine, Zhejiang University, Hangzhou, China;Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, 310009, Hangzhou, Zhejiang Province, China;Institute of Gastroenterology, Zhejiang University, Hangzhou, China;Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, 310009, Hangzhou, Zhejiang Province, China;Institute of Gastroenterology, Zhejiang University, Hangzhou, China;Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China;Research Center of Prevention and Treatment of Senescent Disease, School of Medicine, Zhejiang University, Hangzhou, China;

关键词: Colorectal cancer;    B.adolescentis;    Macrophages;    Decorin;    TLR2;   

DOI  :  10.1186/s13046-023-02746-6

 received in 2023-03-07, accepted in 2023-06-30,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin+ macrophages in colorectal cancer.MethodsThe relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin+ macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin+ macrophages on the CRC tissue.ResultsWe found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin+ macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin+ macrophages and the expression level of TLR2 in tumor tissue of CRC patients.ConclusionsThese results highlight that B. adolescentis induced Decorin+ macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.

【 授权许可】

CC BY   
© Italian National Cancer Institute ‘Regina Elena’ 2023. corrected publication 2023

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