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ZO-1 Intracellular Localization Organizes Immune Response in Non-Small Cell Lung Cancer

Déborah Neyrinck-Leglantier1, Julien Lesage1,2, Silvia Blacher3

  • 1University of Reims Champagne-Ardenne, Inserm UMR-S 1250, SFR CAP-Santé, Reims, France.

Frontiers in Cell and Developmental Biology
|December 23, 2021
PubMed

Insights

Zonula occludens-1 (ZO-1) moving from cell junctions impacts tumor progression by altering immune cell recruitment. This protein

Area of Science:

  • Cell biology
  • Immunology
  • Oncology

Background:

  • Delocalization of zonula occludens-1 (ZO-1) from tight junctions is linked to epithelial cell plasticity during tumor progression.
  • The cytoplasmic-to-nuclear expression of ZO-1 influences the secretion of pro-inflammatory chemokines.

Purpose of the Study:

  • To investigate the role of ZO-1's subcellular localization in modulating immune cell infiltration within the tumor microenvironment.
  • To explore the correlation between ZO-1 expression patterns and immune cell populations in lung cancer.

Main Methods:

  • In vitro studies on chemokine secretion modulated by ZO-1 cyto-nuclear content.
  • In vivo mouse ear sponge assays to assess immune cell recruitment.
  • Analysis of lung cancer tissues for ZO-1 expression and immune cell density (CD8+ T cells, Foxp3+ regulatory T cells).

Main Results:

  • ZO-1 cyto-nuclear expression was found to modulate pro-inflammatory chemokine secretion in vitro.
  • ZO-1 promoted immune cell recruitment in vivo.
  • In lung cancers, high densities of CD8+ cytotoxic T cells and Foxp3+ regulatory T cells correlated with cyto-nuclear ZO-1 expression.

Conclusions:

  • The cyto-nuclear pool of ZO-1 influences the tumor cell secretome, potentially recruiting immune cells.
  • This immune cell recruitment mediated by ZO-1 may create a microenvironment permissive for tumor progression.

Keywords:
ZO-1epithelial plasticityepithelial-mesenchymal transitionimmune infiltratelung cancertumor microenvironment

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