Lei Zhang1,2, John S Yu3,4. 1. Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA. 2. Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China. 3. Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA. john.yu@cshs.org. 4. Cedars-Sinai Medical Center, 127 S. San Vincente Blvd. Suite A6600, Los Angeles, CA, 90048, USA. john.yu@cshs.org.
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.
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.
Authors: Allan B Dietz; Peggy A Bulur; Richard L Emery; Jeffrey L Winters; Dennis E Epps; Abba C Zubair; Stanimir Vuk-Pavlović Journal: Transfusion Date: 2006-12 Impact factor: 3.157
Authors: Tyler J Curiel; Shuang Wei; Haidong Dong; Xavier Alvarez; Pui Cheng; Peter Mottram; Roman Krzysiek; Keith L Knutson; Ben Daniel; Maria Carla Zimmermann; Odile David; Matthew Burow; Alan Gordon; Nina Dhurandhar; Leann Myers; Ruth Berggren; Akseli Hemminki; Ronald D Alvarez; Dominique Emilie; David T Curiel; Lieping Chen; Weiping Zou Journal: Nat Med Date: 2003-04-21 Impact factor: 53.440
Authors: Andrew T Parsa; James S Waldron; Amith Panner; Courtney A Crane; Ian F Parney; Jeffrey J Barry; Kristine E Cachola; Joseph C Murray; Tarik Tihan; Michael C Jensen; Paul S Mischel; David Stokoe; Russell O Pieper Journal: Nat Med Date: 2006-12-10 Impact factor: 53.440
Authors: Haidong Dong; Scott E Strome; Diva R Salomao; Hideto Tamura; Fumiya Hirano; Dallas B Flies; Patrick C Roche; Jun Lu; Gefeng Zhu; Koji Tamada; Vanda A Lennon; Esteban Celis; Lieping Chen Journal: Nat Med Date: 2002-06-24 Impact factor: 53.440