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NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma

Shutao Zheng1, Qing Liu1, Tao Liu2

  • 1Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, PR China; State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Xinjiang Uygur Autonomous Region, Urumqi, PR China.

Biochemical and Biophysical Research Communications
|March 21, 2020
PubMed

Insights

NME4 (Nucleoside Diphosphate Kinase 4) silencing downregulates PD-L1 and inactivates STAT3 in esophageal cancer cells. This suggests NME4 may hinder CD8 T cell infiltration in squamous cell carcinoma.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • NME4 (NME/NM23 Nucleoside Diphosphate Kinase 4) is crucial for nucleoside triphosphate synthesis.
  • The relationship between NME4 and programmed death ligand 1 (PD-L1) is not well understood.
  • PD-L1 plays a significant role in immune evasion within the tumor microenvironment.

Purpose of the Study:

  • To investigate the association between NME4 and PD-L1 expression.
  • To explore the functional impact of NME4 on PD-L1 regulation in squamous cell carcinoma.
  • To determine the potential role of NME4 in immune cell infiltration within the tumor microenvironment.

Main Methods:

  • In vitro experiments involving silencing NME4 in esophageal squamous cell carcinoma (ESCC) cell lines.
  • Analysis of phosphorylated STAT3 (Signal Transducer and Activator of Transcription 3) inactivation.
  • Pearson correlation analysis of NME4 and PD-L1 transcriptomic data in cervical squamous cell carcinoma (CSCC) using the GEPIA database.

Main Results:

  • Silencing NME4 led to significant downregulation of PD-L1 expression in ESCC cell lines.
  • In vitro inactivation of phosphorylated STAT3 at serine 705 was observed upon NME4 silencing.
  • A significant negative correlation between NME4 and PD-L1 expression was found in CSCC patient data.

Conclusions:

  • This study is the first to report NME4's modulation of PD-L1 in squamous cell carcinoma.
  • NME4 may play a role in regulating PD-L1 expression, potentially influencing the tumor immune microenvironment.
  • NME4's activity suggests a mechanism for excluding CD8 T cells from infiltrating squamous cell carcinoma.
Keywords:
GEPIANME4PD-L1STAT3Squamous cell carcinoma

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