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.

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 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 >30% of Bregs, increased melanoma growth, whereas non-B1a B cell transfer, which includes <2% of Bregs, exhibited no effect. In addition, adoptive transfer of B1a B cells from wild-type 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 T helper 1 type cytokine production in tumor-infiltrating CD8+ T cells. Therefore, B1a Bregs can be a potentially novel target for immunotherapy of melanomas.

• Authors: Tadahiro Kobayashi, Kyosuke Oishi, Ai Okamura, Shintaro Maeda, Akito Komuro, Yasuhito Hamaguchi, Manabu Fujimoto, Kazuhiko Takehara, Takashi Matsushita
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 139 Issue 7 Pg. 1535-1544.e1 (07 2019) ISSN: 1523-1747 [Electronic] United States
• PMID: 30836062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Interleukin-10
• PTEN Phosphohydrolase

Topics

• Animals
• B-Lymphocyte Subsets (immunology, transplantation)
• B-Lymphocytes, Regulatory (immunology, transplantation)
• CD8-Positive T-Lymphocytes (immunology)
• Cytokines (metabolism)
• Humans
• Immune Tolerance
• Interleukin-10 (genetics, metabolism)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Melanoma (immunology)
• Melanoma, Experimental
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neoplasms, Experimental
• PTEN Phosphohydrolase (genetics)
• Th1 Cells (immunology)