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Regulatory B cells induced by pancreatic cancer cell-derived interleukin-18 promote immune tolerance via the PD-1/PD-L1 pathway

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单位： [1]Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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关键词： Immune tolerance Interleukin-18 Pancreatic cancer PD-1/PD-L1 pathway Regulatory B cells

摘要：

Dysregulation of regulatory B cells (Bregs), a type of immunosuppressive lymphocyte, are associated with development of autoimmune diseases and cancers. Bregs produce immune tolerance-inducing cell surface molecules and tolerogenic cytokines (interleukin [IL]-10 and transforming growth factor-beta). We previously showed that levels of the inflammatory cytokine IL-18 were increased in patients with pancreatic cancer. In the present study study, we found that pancreatic cancer cellderived IL-18 increases Breg-induced immunosuppression. IL-18 also promoted B-cell proliferation and IL-10 expression in vivo and in vitro. In addition, IL-18 upregulated membrane PD-1 in B cells and inhibited the antibody-dependent cellular cytotoxicity of Tc cells and natural killer cells. Finally, the combination of a natural IL-18 inhibitor (IL-18BP) and a PD-1/PD-L1 inhibitor suppressed tumor growth and metastasis in a murine pancreatic cancer model. Our results show that IL-18 and PD-1/PD-L1 could be therapeutic targets in pancreatic cancer. © Zhao et al.

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出版当年[2017]版：

大类 | 2 区医学

小类 | 2 区肿瘤学 3 区细胞生物学

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第一作者单位： [1]Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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