Open Access

Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment

  • Authors:
    • Mariko Hirai
    • Hiroko Kitahara
    • Yutaka Kobayashi
    • Koroku Kato
    • George Bou-Gharios
    • Hiroyuki Nakamura
    • Shuichi Kawashiri
  • View Affiliations

  • Published online on: December 2, 2016     https://doi.org/10.3892/ijo.2016.3785
  • Pages: 41-48
  • Copyright: © Hirai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly.
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January-2017
Volume 50 Issue 1

Print ISSN: 1019-6439
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Spandidos Publications style
Hirai M, Kitahara H, Kobayashi Y, Kato K, Bou-Gharios G, Nakamura H and Kawashiri S: Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment. Int J Oncol 50: 41-48, 2017
APA
Hirai, M., Kitahara, H., Kobayashi, Y., Kato, K., Bou-Gharios, G., Nakamura, H., & Kawashiri, S. (2017). Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment. International Journal of Oncology, 50, 41-48. https://doi.org/10.3892/ijo.2016.3785
MLA
Hirai, M., Kitahara, H., Kobayashi, Y., Kato, K., Bou-Gharios, G., Nakamura, H., Kawashiri, S."Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment". International Journal of Oncology 50.1 (2017): 41-48.
Chicago
Hirai, M., Kitahara, H., Kobayashi, Y., Kato, K., Bou-Gharios, G., Nakamura, H., Kawashiri, S."Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment". International Journal of Oncology 50, no. 1 (2017): 41-48. https://doi.org/10.3892/ijo.2016.3785