Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers

Yuqiu Xu; Zhuang Wei; Mei Feng; Dexiang Zhu; Shenglin Mei; Zhongen Wu; Qingyang Feng; Wenju Chang; Meiling Ji; Chenglong Liu; Yuanyuan Zhu; Lian Shen; Fan Yang; Yijiao Chen; Yuxiong Feng; Jianmin Xu; Di Zhu

doi:10.1016/j.celrep.2022.111295

Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers

Cell Rep. 2022 Aug 30;40(9):111295. doi: 10.1016/j.celrep.2022.111295.

Authors

Yuqiu Xu¹, Zhuang Wei², Mei Feng³, Dexiang Zhu¹, Shenglin Mei⁴, Zhongen Wu⁵, Qingyang Feng¹, Wenju Chang¹, Meiling Ji¹, Chenglong Liu⁵, Yuanyuan Zhu⁵, Lian Shen⁵, Fan Yang⁵, Yijiao Chen¹, Yuxiong Feng⁶, Jianmin Xu⁷, Di Zhu⁸

Affiliations

¹ Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, Shanghai 200031, China.
³ Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
⁴ Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Science and Technology, Tongji University, Shanghai 200433, China.
⁵ School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201203, China.
⁶ Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, China.
⁷ Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: xujmin@aliyun.com.
⁸ Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: zhudi@fudan.edu.cn.

PMID: 36044847
DOI: 10.1016/j.celrep.2022.111295

Abstract

More than 40% of patients with late-stage colorectal cancer (CRC) develop liver metastasis (LM). Which immune cells play important roles in CRC-LM and contribute to the difference between left-sided CRC (LCC) and right-sided CRC (RCC) remain unclear. By single-cell RNA sequencing (scRNA-seq), we not only find that activated B cells are significantly depleted in CRC with LM, but also find a subtype of B cells developed from activated B cells, namely immature plasma cell population alpha (iMPA), highly correlated with metastasis. Mechanistically, inhibition of the Wnt and transforming growth factor β (TGF-β) pathways in cancer cell promotes activated B cell migration via the SDF-1-CXCR4 axis. This study reveals that B cell subpopulations in the tumor immune microenvironment (TIME) play a key role in CRC-LM as well as in LCC and RCC. The preventive effects of modulating B cell subpopulations in CRC may provide a rationale for subsequent drug development and CRC-LM management.

Keywords: CP: Cancer; SDF-1-CXCR4; Wnt signaling; activated B cells; colorectal cancer; liver metastasis; scRNA-seq; tumor immune microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell* / genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Colorectal Neoplasms* / pathology
Gene Expression Regulation, Neoplastic
Humans
Kidney Neoplasms* / genetics
Liver Neoplasms* / metabolism
Tumor Microenvironment