4.8 Article

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

Journal

CELL REPORTS
Volume 40, Issue 9, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2022.111295

Keywords

colorectal cancer liver metastasis (CRC

Categories

Funding

  1. National Natural Science Foundation of China [31801110, 82072678, 81872895, 82073881, 31701165]
  2. Shanghai Science and Technology Committee Project [19511121300]
  3. Science and Technology Commission of Shanghai [18ZR1403900, 20430713600]
  4. Shanghai Institute of Materia Medica [FU-SIMM20181010]
  5. Fudan University [FU-SIMM20181010]

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This study used single-cell RNA sequencing to investigate the immune cells involved in colorectal cancer liver metastasis. The researchers found that activated B cells were significantly depleted in patients with liver metastasis. They also identified a subtype of B cells called immature plasma cell alpha that was highly correlated with metastasis. Inhibition of the Wnt and TGF-0 pathways in cancer cells promoted the migration of activated B cells. These findings highlight the importance of B cell subpopulations in colorectal cancer liver metastasis and suggest potential strategies for drug development and management.
More than 40% of patients with late-stage colorectal cancer (CRC) develop liver metastasis (LM). Which im-mune 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 0 (TGF-0) pathways in cancer cell pro-motes 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 preven-tive effects of modulating B cell subpopulations in CRC may provide a rationale for subsequent drug develop-ment and CRC-LM management.

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