Analysis of the role and mechanism of regulatory B cells in tumor immunity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15269
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kanazawa University
• Principal Investigator: Kobayashi Tadahiro 金沢大学, 附属病院, 助教 (20746383)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 悪性黒色腫 / 制御性B細胞 / 腫瘍免疫 / IL-10 / B1a B細胞

Outline of Final Research Achievements

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 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 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. Therefore, B1a Bregs can be a potentially novel target for immunotherapy of melanomas.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果より、B細胞のサブセットである制御性B細胞はIL-10を産生することで悪性黒色腫に対する腫瘍免疫反応を抑制していることが示された。このことから、制御性B細胞およびIL-10が悪性黒色腫の新規治療開発のための標的になりうると考えられる。