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Characterization of B cell‐mediated PD‐1/PD‐L1 interaction in pancreatic cancer patients
Author(s) -
Tong DaNian,
Guan Jiao,
Sun JianHua,
Zhao ChongYue,
Chen ShiGeng,
Zhang ZhengYun,
Zhou ZunQiang
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13317
Subject(s) - pancreatic cancer , cd40 , cancer research , cytotoxic t cell , cd8 , pd l1 , chemistry , cancer cell , biology , microbiology and biotechnology , antigen , immune system , in vitro , cancer , medicine , immunotherapy , immunology , biochemistry
Pancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer with one of the worst survival rate of all malignancies. Recent studies have identified that immunosuppressive B cells could employ the PD‐1/PD‐L1 pathway to suppress antitumour T cell responses; hence, we examined the expression and function of PD‐L1 in B cells. We found that the PD‐L1 expression was significantly enriched in tumour‐infiltrating (TI) B cells than in peripheral blood (PB) B cells from the same patients. Additionally, the PB B cells from stage III and stage IV PDAC patients presented significantly higher PD‐L1 than the PB B cells from healthy controls. High PD‐L1 expression in PB B cells could be achieved by stimulation via CpG and less effectively via anti‐BCR plus CD40L, but not by coculture with pancreatic cancer cell lines in vitro. Also, STAT1 and STAT3 inhibition significantly suppressed PD‐L1 upregulation in stimulated B cells. CpG‐stimulated PB B cells could inhibit the IFN‐γ expression and proliferation of CD8 T cells in a PD‐L1‐dependent manner. Also, TI CD8 T cells incubated with whole TI B cells presented significantly lower IFN‐γ expression and lower proliferation, than TI CD8 T cells incubated with PD‐L1 + cell‐depleted TI B cells, suggesting that PD‐L1 + B cells could also suppress CD8 T cells in the tumour. Overall, this study identified that B cells could suppress CD8 T cells via PD‐L1 expression, indicating a novel pathway of immuno‐regulation in pancreatic cancer.