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Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 3/2019

01-07-2019 | Glioma | Laboratory Investigation

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

Authors: Lei Zhang, John S. Yu

Published in: Journal of Neuro-Oncology | Issue 3/2019

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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.
Literature
1.
Johnson DR, O'Neill BP (2012) Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol 107(2):359–364.CrossRefPubMed
2.
Parsa AT, Waldron JS, Panner A et al (2007) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13(1):84–88CrossRefPubMed
3.
4.
Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800CrossRef
5.
6.
Wang Z, Zhang C, Liu X et al (2016) Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma. Oncoimmunology 5(11):e1196310CrossRefPubMedPubMedCentral
7.
Hirano F, Kaneko K, Tamura H et al (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65(3):1089–1096PubMed
8.
Curiel TJ, Wei S, Dong H et al (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562–567CrossRefPubMed
9.
Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465CrossRefPubMedPubMedCentral
10.
11.
Yang S, Chen J, Guo Z et al (2003) Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther 2(1):65–72PubMed
12.
Liang M, Fu J (2008) Triptolide inhibits interferon-gamma-induced programmed death-1-ligand 1 surface expression in breast cancer cells. Cancer Lett 270(2):337–341CrossRefPubMed
13.
Dietz AB, Bulur PA, Emery RL et al (2006) A novel source of viable peripheral blood mononuclear cells from leukoreduction system chambers. Transfusion 46(12):2083–2089CrossRefPubMed
14.
Zhang H, Zhu W, Su X et al (2012) Triptolide inhibits proliferation and invasion of malignant glioma cells. J Neurooncol 109(1):53–62CrossRefPubMed
15.
Sai K, Li WY, Chen YS et al (2014) Triptolide synergistically enhances temozolomide-induced apoptosis and potentiates inhibition of NF-kappaB signaling in glioma initiating cells. Am J Chin Med 42(2):485–503CrossRefPubMed
16.
Flies DB, Han X, Higuchi T et al (2014) Coinhibitory receptor PD-1H preferentially suppresses CD4(+) T cell-mediated immunity. J Clin Invest 124(5):1966–1975CrossRefPubMedPubMedCentral
17.
Mangani D, Weller M, Roth P (2017) The network of immunosuppressive pathways in glioblastoma. Biochem Pharmacol 130:1–9CrossRefPubMed
18.
Nduom EK, Weller M, Heimberger AB (2015) Immunosuppressive mechanisms in glioblastoma. Neuro Oncol 17(Suppl 7):9–14CrossRef
19.
Wintterle S, Schreiner B, Mitsdoerffer M et al (2003) Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res 63(21):7462–7467PubMed
20.
Yao Y, Tao R, Wang X, Wang Y, Mao Y, Zhou LF (2009) B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells. Neuro Oncol 11(6):757–766CrossRefPubMedPubMedCentral
21.
Zhang L, Zhang Z, Liu Y, Xue Y, Parney I (2015) Programmed death-ligand 1 (PD-L1) may play a role in malignant glioma infiltration. Med Hypotheses 85(2):127–129CrossRefPubMed
22.
Trickett A, Kwan YL (2003) T cell stimulation and expansion using anti-CD3/CD28 beads. J Immunol Methods 275(1–2):251–255CrossRefPubMed
23.
Pene J, Rahmoun M, Temmerman S, Yssel H (2003) Use of anti-CD3/CD28 mAb coupled magnetic beads permitting subsequent phenotypic analysis of activated human T cells by indirect immunofluorescence. J Immunol Methods 283(1–2):59–66CrossRefPubMed
Metadata
Title
Triptolide reverses helper T cell inhibition and down-regulates IFN-γ induced PD-L1 expression in glioma cell lines
Authors
Lei Zhang
John S. Yu
Publication date
01-07-2019
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-019-03193-0

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Correction

Correction to: Phase I-II trial of imatinib mesylate (Gleevec; STI571) in treatment of recurrent oligodendroglioma and mixed oligoastrocytoma. North central cancer treatment group study N0272 (ALLIANCE/NCCTG)