IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer
2019
Abstract Background Tumor immune reactions not only provide host defense but also accelerate tumor immune escape and phenotype switching. Here, we examined the association of programmed cell death ligand 1 (PD-L1) expression with epithelial-mesenchymal transition (EMT)–associated markers in pancreatic ductal adenocarcinoma (PDA) within the context of the tumor microenvironment. Materials and methods PDA samples from 36 patients were analyzed for PD-L1, vimentin, E-cadherin, and Snail expressions and for PDA cell and immune cell infiltration. PD-L1 expression and EMT in PDA cell lines under conditions of altering interferon gamma (IFN-γ) signals were also assessed. Results Immunohistochemistry revealed a significant correlation between vimentin and PD-L1 expression, whereas double staining showed them to be simultaneously expressed by PDA cells. Positive vimentin expression was associated with the infiltration of a lower number of CD8 + T cells and a higher number of FoxP3 + cells and poor patient prognosis ( P = 0.03). PDA tumor cells promoted PD-L1 expression and EMT under the presence of IFN-γ, which was inhibited by the signal transducer and activator of transcription (STAT)1 small interfering RNA. Conclusions Strong correlations were observed between PD-L1 expression, EMT, and the immunosuppressive tumor microenvironment. Targeting STAT1 combined with PD-1/PD-L1 immunotherapy may improve outcomes for patients with PDA.
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