Triptolide reverses helper T cell inhibition and down-regulates IFN-γ induced PD-L1 expression in glioma cell lines
Authors:
- 31 May 2019
- journal article
- research article
- Published by Springer Nature in Journal of Neuro-Oncology
- Vol. 143 (3) , 429-436
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
Funding Information
- Milken Family Foundation (Fastercures)
This publication has 23 references indexed in Scilit:
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerNew England Journal of Medicine, 2012
- Triptolide inhibits proliferation and invasion of malignant glioma cellsJournal of Neuro-Oncology, 2012
- B7-H1 Expressed by Activated CD8 T Cells Is Essential for Their SurvivalThe Journal of Immunology, 2011
- Glioblastoma survival in the United States before and during the temozolomide eraJournal of Neuro-Oncology, 2011
- B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cellsNeuro-Oncology, 2009
- Triptolide inhibits interferon-γ-induced programmed death-1-ligand 1 surface expression in breast cancer cellsCancer Letters, 2008
- Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in gliomaNature Medicine, 2006
- A novel source of viable peripheral blood mononuclear cells from leukoreduction system chambersTransfusion, 2006
- Blockade of B7-H1 improves myeloid dendritic cell–mediated antitumor immunityNature Medicine, 2003
- Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasionNature Medicine, 2002