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2018 ; 9
(19
): 14803-14814
Nephropedia Template TP
gab.com Text
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English Wikipedia
Regulatory B cells induced by pancreatic cancer cell-derived interleukin-18
promote immune tolerance via the PD-1/PD-L1 pathway
#MMPMID29599908
Zhao Y
; Shen M
; Feng Y
; He R
; Xu X
; Xie Y
; Shi X
; Zhou M
; Pan S
; Wang M
; Guo X
; Qin R
Oncotarget
2018[Mar]; 9
(19
): 14803-14814
PMID29599908
show ga
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.