[en] 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 cell-derived 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Zhao, Yan; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Shen, Ming; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Feng, Yecheng; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
He, Ruizhi; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xu, Xiaodong; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Xie, Yu; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Shi, Xiuhui ; Université de Liège - ULiège > Département de pharmacie ; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Zhou, Min; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Pan, Shutao; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Wang, Min; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Guo, Xingjun; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Qin, Renyi; Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Language :
English
Title :
Regulatory B cells induced by pancreatic cancer cell-derived interleukin-18 promote immune tolerance via the PD-1/PD-L1 pathway.
We sincerely thank the staff of the Huazhong University of Science and Technology Public Experimental Platform. This study was funded by The National Natural Science Foundation of China (Grants No. 81272659 and 81772950 to Renyi Qin, Grant No. 81602475 to Xingjun Guo Grant No. 81772950 to Min Wang) and the Research Fund of Young Scholars for the Doctoral Program of Higher Education of China (No. 20110142120014 to Renyi Qin, No. 20120142110055 to Min Wang)This study was funded by The National Natural Science Foundation of China (Grants No. 81272659 and 81772950 to Renyi Qin, Grant No. 81602475 to Xingjun Guo Grant No. 81772950 to Min Wang) and the Research Fund of Young Scholars for the Doctoral Program of Higher Education of China (No. 20110142120014 to Renyi Qin, No. 20120142110055 to Min Wang).
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