Activation of glioma cells generates immune tolerant NKT cells

J Biol Chem. 2014 Dec 12;289(50):34595-600. doi: 10.1074/jbc.M114.614503. Epub 2014 Oct 23.

Abstract

Therapeutic outcomes of glioma are currently not encouraging. Tumor tolerance plays an important role in the pathogenesis of glioma. It is reported that micro RNAs (miR) are associated with tumor development. This study aims to investigate the role of miR-92a in the development of tolerant natural killer T (NKT) cells. In this study, U87 cells (a human glioma cell line) and primary glioma cells were prepared. The assessment of miR-92a was performed by real time RT-PCR. The expression of interleukin (IL)-10 and IL-6 in NKT cells was evaluated by flow cytometry. Results showed that abundant IL-6(+) IL-10(+) NKT cells were detected in glioma tissue. Cultures of glioma cells and NKT cells induced the expression of IL-6 and IL-10 in NKT cells. Glioma cells expressed miR-92a; the latter played a critical role in the induction of IL-6 and IL-10 expression in NKT cells. The expression of the antitumor molecules, including perforin, Fas ligand, and interferon-γ, was significantly attenuated compared with control NKT cells. The IL-6(+) IL-10(+) NKT cells showed less capability in the induction of apoptosis in glioma cells, but showed the immune suppressor functions on CD8(+) T cell activities. We conclude that glioma-derived miR-92a induces IL-6(+) IL-10(+) NKT cells; this fraction of NKT cells can suppress cytotoxic CD8(+) T cells.

Keywords: Cellular Immune Response; Glioblastoma; Lymphocyte; RNA; Tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / immunology
  • Glioma / genetics
  • Glioma / immunology
  • Glioma / pathology*
  • Humans
  • Immune Tolerance*
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • MicroRNAs / genetics
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism

Substances

  • Interleukin-6
  • MIRN92 microRNA, human
  • MicroRNAs
  • Interleukin-10