Regulatory B1a cells suppress melanoma tumor immunity via IL-10 production and inhibiting Th1 cytokine production in tumor-infiltrating CD8+ T cells

Abstract In tumor immunity, the participation of IL-10-producing regulatory B cells (Bregs), which play an important role in suppressing immune responses, is unclear. In this study, we demonstrated an increase in B16F10 melanoma growth and a decrease in the proportion of IFN-γ- and TNF-α-secreting tumor-infiltrating CD8 + T cells in B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice in which Bregs were expanded. The number of tumor-infiltrating Bregs significantly increased in B cell-specific PTEN-deficient mice. More than 50% of tumor-infiltrating B cells consisted of Bregs, predominantly CD19 + CD5 + CD43 + B1a Bregs, in both B cell-specific PTEN-deficient and control mice. Adoptive B1a B cell transfer, which includes more than 30% of Bregs, increased melanoma growth, whereas non-B1a B cell transfer, which includes less than 2% of Bregs, exhibited no effect. In addition, adoptive transfer of B1a B cells from WT mice, but not IL-10 -/- mice, exacerbated B16F10 melanoma growth. The current study indicates that B1a Bregs negatively regulate anti-melanoma immunity by producing IL-10 and reducing Th1 cytokine production in tumor-infiltrating CD8 + T cells. Therefore, B1a Bregs can be a potentially novel target for immunotherapy of melanomas.