The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer

  • Authors:
    • Nan Zhang
    • Yuanyuan Zeng
    • Wenwen Du
    • Jianjie Zhu
    • Dan Shen
    • Zeyi Liu
    • Jian-An Huang
  • View Affiliations

  • Published online on: July 26, 2016     https://doi.org/10.3892/ijo.2016.3632
  • Pages: 1360-1368
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Abstract

Negative regulation of the signal mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway can effectively inhibit the function of T and B cells, which play a key role in the regulation of immune response. Recently, emerging evidence has suggested that the expression of PD-L1 is related to the mutation status of the epidermal growth factor receptor (EGFR). Moreover, the activation of the EGFR signaling pathway can induce expression of PD-L1. In the present study, we demonstrated that activated EGFR can upregulate the expression of PD-L1 through the interleukin 6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway in non-small cell lung cancer (NSCLC) cells. Cells treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can downregulate the activation of the IL-6/JAK/STAT3 pathway, which subsequently reduces the expression of PD-L1. Furthermore, silencing of PD-L1 expression in NSCLC cells correlated with inhibition of cell proliferation and enhanced tumor cell apoptosis. In summary, our research indicates that EGFR is involved in the regulation of PD-L1 expression and cell proliferation via the IL-6/JAK/STAT3 signaling pathway in NSCLC. The present study suggests the potential of combined targeted therapy with immunotherapy in the treatment of NSCLC.
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October-2016
Volume 49 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhang N, Zeng Y, Du W, Zhu J, Shen D, Liu Z and Huang J: The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer. Int J Oncol 49: 1360-1368, 2016
APA
Zhang, N., Zeng, Y., Du, W., Zhu, J., Shen, D., Liu, Z., & Huang, J. (2016). The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer. International Journal of Oncology, 49, 1360-1368. https://doi.org/10.3892/ijo.2016.3632
MLA
Zhang, N., Zeng, Y., Du, W., Zhu, J., Shen, D., Liu, Z., Huang, J."The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer". International Journal of Oncology 49.4 (2016): 1360-1368.
Chicago
Zhang, N., Zeng, Y., Du, W., Zhu, J., Shen, D., Liu, Z., Huang, J."The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer". International Journal of Oncology 49, no. 4 (2016): 1360-1368. https://doi.org/10.3892/ijo.2016.3632