Triptolide reverses helper T cell inhibition and down-regulates IFN-γ induced PD-L1 expression in glioma cell lines

J Neurooncol. 2019 Jul;143(3):429-436. doi: 10.1007/s11060-019-03193-0. Epub 2019 May 31.

Abstract

Purpose: Immunosuppression is one of hallmark features in many cancers including glioma. Triptolide, a natural compound purified from the Chinese herb Tripterygium wilfordii, has been reported to inhibit PD-L1 otherwise known as the B7 homolog 1 (B7-H1) expression in breast cancer. The purpose of this paper is to test the effects of Triptolide on T cell inhibition in glioma cells.

Methods: We labeled T cells and cocultured with Interferon-γ (IFN-γ) and Triptolide treated glioma cells. The effect on inhibition of T cells as well as subtypes of T cells was measured by Flow Cytometry. We also tested the expression of PD-L1 in six glioma cell lines.

Results: We found that Triptolide could reverse T cell inhibition especially CD4+ T cell and induced IFN-γ secretion. In addition, Triptolide could also induce interleukin-2 secretion and overcome interleukin-10 inhibition caused by glioma cells under IFN-γ treated condition. Triptolide could also down-regulate IFN-γ induced PD-L1 surface expression in glioma cells.

Conclusions: These results suggest that Triptolide may be used to reverse CD4+ T cell inhibition caused by glioma cells and is an alternative candidate for targeting PD-L1, one of the checkpoint inhibitors for the treatment of glioma.

Keywords: CD4+ T cells; Glioma; PD-L1; Triptolide.

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Coculture Techniques
  • Diterpenes / pharmacology*
  • Down-Regulation
  • Epoxy Compounds / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioma / drug therapy*
  • Glioma / immunology
  • Glioma / metabolism
  • Humans
  • Interferon-gamma / pharmacology*
  • Phenanthrenes / pharmacology*
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Alkylating
  • B7-H1 Antigen
  • CD274 protein, human
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • triptolide
  • Interferon-gamma