Temozolomide increases MHC-I expression via NF-κB signaling in glioma stem cells

Cell Biol Int. 2017 Jun;41(6):680-690. doi: 10.1002/cbin.10773. Epub 2017 May 2.

Abstract

Gliomas are the most common and primary tumors of the central nervous system in adults. Temozolomide (TMZ) is the main drug used to treat glioma; however, prognosis remains poor for most patients. Glioma stem cells (GSCs) are thought to enable glioma initiation and evasion from immune surveillance; their immunogenicity can be determined by expression of major histocompatibility complex (MHC)-I. The present study investigated the effect of TMZ on MHC-I expression in GSCs. Glioma spheres were cultured in serum-free medium containing epidermal growth factor, basic fibroblast growth factor, and B27; MHC-I expression was detected by immunocytochemistry, quantitative real-time PCR, and flow cytometry. Nuclear factor (NF)-κB expression in glioma stem cells was detected by Western blot. TMZ enhanced MHC-I expression in GSCs, and NF-κB was activated. TMZ treatment increased MHC-I expression via modulation of NF-κB signaling in GSCs. In addition to being a chemotherapeutic agent, TMZ may also serve as an immunomodulatory agent in the treatment of glioma patients.

Keywords: MHC-I; T cells; flow cytometry; immunology; stem cells.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / metabolism
  • Dacarbazine / pharmacology
  • Drug Synergism
  • Genes, MHC Class I / drug effects*
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Humans
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neoplastic Stem Cells / metabolism
  • Primary Cell Culture / methods
  • Signal Transduction / drug effects
  • Stem Cells / drug effects
  • Temozolomide

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Dacarbazine
  • Temozolomide