(E) Human peripheral CD3 + T cells were cocultured with si-scr or si-HMGB1 EV-treated neutrophils in the presence or absence of PD-L1 antibody. (D) The expression of signal transducer and activator of transcription (STAT)3 and p-STAT3 in neutrophils treated with si-scr or si-HMGB1 EVs for 12 h was determined by Western blot. Protein and gene levels of PD-L1 on neutrophils exposed to si-scr or si-HMGB1 EVs for 12 h were determined by flow cytometry (B) and qRT-PCR (C). (A) The expression of HMGB1 in scramble and HMGB1 siRNA-transfected BGC cells and BGC-EVs was determined by Western blot and qRT-PCR. Gastric cancer (GC)-derived extracellular vesicles (EVs) induce programmed death-ligand 1 (PD-L1) expression and immunosuppressive function in neutrophils through high-mobility group box 1 (HMGB1). Taken together, our results indicate that EVs from the GC microenvironment induce PD-L1 expression on neutrophils to suppress T-cell immunity, which provides a new insight into the pro-tumor roles of neutrophils in GC and sheds light on the multifaceted roles of EVs in orchestrating an immunosuppressive microenvironment.Įxtracellular vesicles gastric cancer immune suppression neutrophils programmed death-ligand 1 (PD-L1).Ĭopyright © 2020 Shi, Zhang, Mao, Jiang, Liu, Shi, Ji, Xu, Qian and Zhang. Furthermore, GC tissue-derived EVs also showed similar effects. GC-EV-elicited neutrophils suppressed T cell proliferation, activation, and function in vitro, which could be antagonized by a specific PD-L1 antibody. Blocking STAT3 pathway and silencing HMGB1 reversed GC-EV-induced PD-L1 expression on neutrophils. GC-EVs transported high-mobility group box-1 (HMGB1) to activate signal transducer and activator of transcription 3 (STAT3) and upregulate PD-L1 gene expression in neutrophils. Herein, we reported that gastric cancer cell-derived EVs (GC-EVs) induced the expression of programmed death-ligand 1 (PD-L1) on neutrophils.

We have previously shown that tumor extracellular vesicles (EVs) could induce pro-tumor activation of neutrophils however, the role of tumor EV-elicited neutrophils in tumor immunity remains unclear. Neutrophils are prominent components of solid tumors and exhibit distinct phenotypes in different tumor milieu.

Gc pro box and gc pro key