Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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.
Cell Rep. 2022 Aug 30;40(9):111295. doi: 10.1016/j.celrep.2022.111295.
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.
超过 40%的晚期结直肠癌 (CRC) 患者会发生肝转移 (LM)。哪些免疫细胞在 CRC-LM 中发挥重要作用，以及它们如何导致左半结直肠癌 (LCC) 和右半结直肠癌 (RCC) 之间的差异尚不清楚。通过单细胞 RNA 测序 (scRNA-seq)，我们不仅发现 LM 结直肠癌中活化的 B 细胞明显耗竭，而且还发现了一种源自活化 B 细胞的 B 细胞亚型，即幼稚浆细胞群体 alpha (iMPA)，与转移高度相关。在机制上，癌细胞中 Wnt 和转化生长因子 β (TGF-β) 通路的抑制通过 SDF-1-CXCR4 轴促进活化 B 细胞迁移。这项研究揭示了肿瘤免疫微环境 (TIME) 中的 B 细胞亚群在 CRC-LM 以及 LCC 和 RCC 中发挥关键作用。调节 CRC 中 B 细胞亚群的预防作用可能为后续药物开发和 CRC-LM 管理提供依据。
