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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
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