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Induction of PD-L1 expression by epidermal growth factor receptor–mediated signaling in esophageal squamous cell carcinoma

Authors Zhang W, Pang Q, Yan C, Wang Q, Yang J, Yu S, Liu X, Yuan Z, Wang P, Xiao Z

Received 4 August 2016

Accepted for publication 18 November 2016

Published 13 February 2017 Volume 2017:10 Pages 763—771

DOI https://doi.org/10.2147/OTT.S118982

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Carlos Vigil Gonzales

Wencheng Zhang,1 Qingsong Pang,1 Cihui Yan,2 Qifeng Wang,3 Jingsong Yang,3 Shufei Yu,3 Xiao Liu,3 Zhiyong Yuan,1 Ping Wang,1 Zefen Xiao3

1Department of Radiation Oncology, 2Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

Purpose: The purpose of this study was to investigate the potential effect of activation of epidermal growth factor receptor (EGFR) signaling pathway on the expression of programmed death-ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) cells with EGFR overexpression.
Methods: Flow cytometry and Western blot methods were used to assess PD-L1 expression on ESCC cells when EGFR signaling pathway was activated by epidermal growth factor (EGF) with or without EGFR-specific inhibitor AG-1478, and then EGFR signaling array was applied to analyze the potential signaling pathways involved.
Results: This study found that PD-L1 expression increased significantly in an EGFR-dependent manner by the activation of EGFR signaling and decreased sharply when EGFR signaling was blocked. The upregulated expression of PD-L1 was not associated with EGFR-STAT3 signaling pathway, but may be affected by EGFR–PI3K–AKT, EGFR–Ras–Raf–Erk, and EGR–PLC-γ signaling pathways.
Conclusion: The expression of PD-L1 can be regulated by EGFR signaling activation in ESCC, which indicates an important role for EGFR-mediated immune escape and potential molecular pathways for EGFR-targeted therapy and immunotherapy.

Keywords:
epidermal growth factor receptor, programmed death-ligand 1, esophageal squamous cell carcinoma, immune checkpoint

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