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

Abstract

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 CD19^loCD27^hi plasmablasts, was enriched in the colorectal tumor microenvironment. This CD19^loCD27^hi plasmablast subset presented high interleukin 10 (IL-10) expression but not transforming growth factor-β (TGF-β) secretion. Phenotypically, the tumor-infiltrating IL-10⁺ CD19^loCD27^hi plasmablasts presented lower CD24, CD38, and IgA, and higher Tim-1 and IgG expression compared to the IL-10^- CD19^loCD27^hi plasmablasts. The tumor-infiltrating IL-10⁺ CD19^loCD27^hi 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, CD19^loCD27^hi 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, CD19^loCD27^hi plasmablasts make up a large percentage in tumor-infiltrating lymphocytes and possess potent immunoregulatory functions, and thus could be utilized in future therapeutic strategies.

Keywords: Colorectal cancer; Immune response; Plasmablast.