IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer

Daisuke Imai, Tomoharu Yoshizumi, Shinji Okano, shinji itoh, Toru Ikegami, Noboru Harada, Shinichi Aishima, Yoshinao Oda, Yoshihiko Maehara

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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.

Original languageEnglish
Pages (from-to)115-123
Number of pages9
JournalJournal of Surgical Research
Volume240
DOIs
Publication statusPublished - Aug 1 2019

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Epithelial-Mesenchymal Transition
Pancreatic Neoplasms
Interferon-gamma
Adenocarcinoma
Cell Death
Ligands
Vimentin
Tumor Microenvironment
CD274 Antigen
STAT1 Transcription Factor
Tumor Escape
Snails
Cadherins
Immunosuppressive Agents
Immunotherapy
Small Interfering RNA
Neoplasms
Cell Count
Immunohistochemistry
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer. / Imai, Daisuke; Yoshizumi, Tomoharu; Okano, Shinji; itoh, shinji; Ikegami, Toru; Harada, Noboru; Aishima, Shinichi; Oda, Yoshinao; Maehara, Yoshihiko.

In: Journal of Surgical Research, Vol. 240, 01.08.2019, p. 115-123.

Research output: Contribution to journalArticle

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AU - itoh, shinji

AU - Ikegami, Toru

AU - Harada, Noboru

AU - Aishima, Shinichi

AU - Oda, Yoshinao

AU - Maehara, Yoshihiko

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