Colorectal tumors are enriched with regulatory plasmablasts with capacity in suppressing T cell inflammation

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Inflammation plays a critical role in the initiation of colorectal cancer but is also required to mediate antitumor immunity in established tumors. Therefore, identifying the cellular and molecular components in colorectal tumors is necessary for the understanding of tumor progression and the development of novel treatment strategies. In this study, we demonstrated that a specific subtype of regulatory B cells, the CD19loCD27hi plasmablasts, was enriched in the colorectal tumor microenvironment. This CD19loCD27hi plasmablast subset presented high interleukin 10 (IL-10) expression but not transforming growth factor-β (TGF-β) secretion. Phenotypically, the tumor-infiltrating IL-10+ CD19loCD27hi plasmablasts presented lower CD24, CD38, and IgA, and higher Tim-1 and IgG expression compared to the IL-10 CD19loCD27hi plasmablasts. The tumor-infiltrating IL-10+ CD19loCD27hi plasmablasts were found to be gut-homing due to their higher expression of α4β7 while peripheral blood B cells did not show the same characteristic. When cocultured with autologous T cells, CD19loCD27hi plasmablasts demonstrated potent activity in suppressing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) expression but did not promote Foxp3 expression. Overall, this study demonstrate that in colorectal cancer, CD19loCD27hi plasmablasts make up a large percentage in tumor-infiltrating lymphocytes and possess potent immunoregulatory functions, and thus could be utilized in future therapeutic strategies.HighlightsResected colorectal tumors were enriched with IL-10-secreting plasmablasts.IL-10-secreting plasmablasts displayed different surface markers.IL-10-secreting plasmablasts were gut-homing.IL-10-secreting plasmablasts suppressed proinflammatory cytokine secretion.IL-10-secreting plasmablasts did not support the upregulation of Foxp3 in Tregs.

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