CD19 + CD24 hi CD38 hi Bregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer

Weiwei Wang; Xiangliang Yuan; Hui Chen; Guohua Xie; Yanhui Ma; Yingxia Zheng; Yunlan Zhou; Lisong Shen

doi:10.18632/oncotarget.5588

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Research Papers:

CD19⁺CD24^hiCD38^hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer

Weiwei Wang, Xiangliang Yuan, Hui Chen, Guohua Xie, Yanhui Ma, Yingxia Zheng, Yunlan Zhou and Lisong Shen _

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Oncotarget. 2015; 6:33486-33499. https://doi.org/10.18632/oncotarget.5588

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Abstract

Weiwei Wang1, Xiangliang Yuan1, Hui Chen1, Guohua Xie1, Yanhui Ma1, Yingxia Zheng1, Yunlan Zhou1 and Lisong Shen1

1 Department of Clinical Laboratory, Xinhua Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Correspondence to:

Lisong Shen, email:

Keywords: gastric cancer, regulatory B cells, IL-10, TGF-β, regulatory T cells, immune escape

Received: January 30, 2015 Accepted: August 23, 2015 Published: September 10, 2015

Abstract

Regulatory B cells (Bregs) play a critical role in inflammation and autoimmune disease. We characterized the role of Bregs in the progression of gastric cancer. We detected an increase in Bregs producing IL-10 both in peripheral blood mononuclear cells (PBMCs) and in gastric tumors. Multicolor flow cytometry analysis revealed that a subset of CD19+CD24hiCD38hi B cells produces IL-10. Functional studies indicated that increased Bregs do not inhibit the proliferation of CD3+T cells or CD4+ helper T cells (Th cells). However, Bregs do suppress the secretion of IFN-γ and TNF-α by CD4+Th cells. CD19+CD24hiCD38hiBregs were also found to correlate positively with CD4+FoxP3+ regulatory T cells (Tregs). Neutralization experiments showed that Bregs convert CD4+CD25- effector T cells to CD4+FoxP3+Tregs via TGF-β1. Collectively, these findings demonstrate that increased Bregs play a immunosuppressive role in gastric cancer by inhibiting T cells cytokines as well as conversion to Tregs. These results may provide new clues about the underlying mechanisms of immune escape in gastric cancer.

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Research Papers:

CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer

Abstract

CD19⁺CD24^hiCD38^hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer