4.5 Article

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

Journal

JOURNAL OF NEURO-ONCOLOGY
Volume 143, Issue 3, Pages 429-436

Publisher

SPRINGER
DOI: 10.1007/s11060-019-03193-0

Keywords

Triptolide; CD4+T cells; PD-L1; Glioma

Funding

  1. FasterCures, a center of the Milken Institute
  2. National Institutes of Health [NS048959]

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PurposeImmunosuppression 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.MethodsWe labeled T cells and cocultured with Interferon- (IFN-) 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.ResultsWe found that Triptolide could reverse T cell inhibition especially CD4+ T cell and induced IFN- secretion. In addition, Triptolide could also induce interleukin-2 secretion and overcome interleukin-10 inhibition caused by glioma cells under IFN- treated condition. Triptolide could also down-regulate IFN- induced PD-L1 surface expression in glioma cells.ConclusionsThese 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.

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