Gene expression profiling of CD8+ T cells induced by ovarian cancer cells suggests a possible mechanism for CD8+ Treg cell production

Cell Prolif. 2016 Dec;49(6):669-677. doi: 10.1111/cpr.12294. Epub 2016 Sep 19.

Abstract

Objectives: The aim of this study was to investigate a possible mechanism of CD8+ regulatory T-cell (Treg) production in an ovarian cancer (OC) microenvironment.

Materials and methods: Agilent microarray was used to detect changes in gene expression between CD8+ T cells cultured with and without the SKOV3 ovarian adenocarcinoma cell line. QRT-PCR was performed to determine glycolysis gene expression in CD8+ T cells from a transwell culturing system and OC patients. We also detected protein levels of glycolysis-related genes using Western blot analysis.

Results: Comparing gene expression profiles revealed significant differences in expression levels of 1420 genes, of which 246 were up-regulated and 1174 were down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that biological processes altered in CD8+ Treg are particularly associated with energy metabolism. CD8+ Treg cells induced by co-culture with SKOV3 had lower glycolysis gene expression compared to CD8+ T cells cultured alone. Glycolysis gene expression was also decreased in the CD8+ T cells of OC patients.

Conclusions: These findings provide a comprehensive bioinformatics analysis of DEGs in CD8+ T cells cultured with and without SKOV3 and suggests that metabolic processes may be a possible mechanism for CD8+ Treg induction.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Line, Tumor
  • Energy Metabolism
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Glycolysis
  • Humans
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Ovary / metabolism
  • Ovary / pathology*
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology