The mechanism of de novo expression of programmed cell death-ligand 1 in squamous cell carcinoma of the lung

  • Authors:
    • Tomoyuki Igarashi
    • Koji Teramoto
    • Mitsuaki Ishida
    • Jun Hanaoka
    • Yataro Daigo
  • View Affiliations

  • Published online on: August 3, 2017     https://doi.org/10.3892/or.2017.5876
  • Pages: 2189-2196
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Abstract

Immune checkpoint mechanisms such as the programmed cell death-ligand 1-programmed cell death 1 (PD‑L1-PD‑1) axis are utilized by tumor cells to evade the cytotoxicity of effector immune cells. However, environmental factors responsible for the expression of PD‑L1 on tumor cells remain to be fully elucidated. We hypothesized that an immunological interaction with tumor-infiltrating CD8+ lymphocytes (CD8+ TILs) would contribute to PD‑L1 expression in tumor cells. To verify this hypothesis, we examined the effect of interferon-γ (IFN-γ), a cytokine secreted by CD8+ TILs, on PD‑L1 expression in pulmonary squamous cell carcinomas in vitro. We also evaluated the expression of PD‑L1 and major histocompatibility complex (MHC) class I molecules on tumor cells and CD8+ TILs in squamous cell carcinomas of the lung (n=77) by immunohistochemistry. IFN-γ upregulated PD‑L1 expression on pulmonary squamous carcinoma cells, and the reaction was reversible. In cases where which MHC class I molecule-positive tumor cells were dominant (n=72, 93.5%), cases in which PD‑L1-positive tumor cells were dominant (PD‑L1+ tumor cell‑dominant cases; n=45) were more frequently observed than PD‑L1-negative tumor cell‑dominant cases (n=27) (P=0.006). The number of CD8+ TILs was significantly higher in PD‑L1+ tumor cell‑dominant cases compared with PD‑L1- tumor cell‑dominant cases (P=0.005). These data suggest that the de novo expression of PD‑L1 on tumor cells is upregulated by IFN-γ secreted from CD8+ TILs upon recognition of the tumor cells with an MHC class I molecule.
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October-2017
Volume 38 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Igarashi T, Teramoto K, Ishida M, Hanaoka J and Daigo Y: The mechanism of de novo expression of programmed cell death-ligand 1 in squamous cell carcinoma of the lung. Oncol Rep 38: 2189-2196, 2017
APA
Igarashi, T., Teramoto, K., Ishida, M., Hanaoka, J., & Daigo, Y. (2017). The mechanism of de novo expression of programmed cell death-ligand 1 in squamous cell carcinoma of the lung. Oncology Reports, 38, 2189-2196. https://doi.org/10.3892/or.2017.5876
MLA
Igarashi, T., Teramoto, K., Ishida, M., Hanaoka, J., Daigo, Y."The mechanism of de novo expression of programmed cell death-ligand 1 in squamous cell carcinoma of the lung". Oncology Reports 38.4 (2017): 2189-2196.
Chicago
Igarashi, T., Teramoto, K., Ishida, M., Hanaoka, J., Daigo, Y."The mechanism of de novo expression of programmed cell death-ligand 1 in squamous cell carcinoma of the lung". Oncology Reports 38, no. 4 (2017): 2189-2196. https://doi.org/10.3892/or.2017.5876