Tumor-infiltrated activated B cells suppress liver metastasis of colorectal cancers
Yuqiu Xu, Zhuang Wei, Mei Feng, Dexiang Zhu, 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, Di Zhu
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.