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

• 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 悪性黒色腫 / 制御性B細胞 / 腫瘍免疫 / IL-10 / B1a B細胞 / B細胞 / 免疫療法

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.

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。

Research Products

• [Journal Article] Regulatory B1a Cells Suppress Melanoma Tumor Immunity via IL-10 Production and Inhibiting T Helper Type 1 Cytokine Production in Tumor-Infiltrating CD8+ T Cells. (2019)
  • Author(s): Tadahiro Kobayashi, Kyosuke Oishi, Ai Okamura, Shintaro Maeda, Akito Komuro, Yasuhito Hamaguchi, Manabu Fujimoto, Kazuhiko Takehara, and Takashi Matsushita
  • Journal Title: Journal of Investigative Dermatology Volume: 139 Issue: 7 Pages: 1535-1544
  • DOI: 10.1016/j.jid.2019.02.016
  • Peer Reviewed
• [Presentation] Regulatory B1a Cells Suppress Melanoma Tumor Immunity via IL-10 Production and Inhibiting Th1 Cytokine Production by CD8+ T Cells (2020)
  • Author(s): Tadahiro Kobayashi
  • Organizer: 日本研究皮膚科学会 第45回年次学術大会・総会
  • Int'l Joint Research
• [Presentation] 悪性黒色腫における制御性B細胞の役割についての解析 (2018)
  • Author(s): 小林忠弘、松下貴史、濱口儒人、藤本学、竹原和彦
  • Organizer: 第34回日本皮膚悪性腫瘍学会学術大会
• [Presentation] Tumor-infiltrating CD5+ regulatory B1 cells suppress melanoma tumor immunity via inhibiting cytokine production of tumor-infiltrating CD8+ T cells (2018)
  • Author(s): Tadahiro Kobayashi, Takashi Matsushita, Yasuhito Hamaguchi, Manabu Fujimoto, and Kazuhiko Takehara
  • Organizer: International Investigative Dermatology 2018
  • Int'l Joint Research