Characterization of intratumoral and circulating IL-10-producing B cells in gastric cancer

The tumor microenvironment harbors multiple immunosuppressive mechanisms, many of which involve suppressive immune cells. B regulatory (Breg) cells, as critical regulators of immune responses, were investigated in patients with gastric carcinoma. In the present study, the B cells that expressed IL-10 were highly enriched in tumor-infiltrating B cells, and could also be found at reduced frequencies in circulating B cells. These cells expressed high CD19 and CD20, and were almost exclusively CD27(+) CD10(-) The IL-10 expression was significantly higher in CD27(+) CD10(-)-sorted B cells than in CD27(-) CD10(-)-sorted B cells. In an in vitro coculture of B cells and autologous T cells, CD27(+) CD10(-) B cells were capable of reducing the levels of CD4 T cell-mediated IFN gamma, TNF, and IL-17 expression and the levels of CD8 T cell-mediated IFN gamma and TNF expression. These regulatory effects were dependent on IL-10 as well as CD80/CD86. Interestingly, CD27(+) CD10(-) B cells also significantly elevated IL-10 production from CD4 and CD8 T cells in an IL-10-dependent manner. Overall, we here report enrichment of IL-10-expressing CD27(+) CD10(-) B cells in the intratumoral environment, which could significantly alter the cytokine production profile by CD4 and CD8 T cells.