Induction of specific T helper-9 cells to inhibit glioma cell growth
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Haiyan Zheng1, Baohua Yang2, Dedong Xu4, Wenbo Wang2, Jie Tan3, Liyuan Sun3, Qinghua Li3, Li Sun3, Xuewei Xia2,3
1Department of Neurosurgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, Zhejiang, China
2Department of Neurosurgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, China
3Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, 541001, China
4Department of Neurosurgery, Hainan General Hospital, Haikou, 570311, China
Xuewei Xia, email: [email protected]
Keywords: glioma, immunotherapy, staphylococcal enterotoxin B, interleukin-9, T helper-9 cell
Received: June 20, 2016 Accepted: December 05, 2016 Published: December 16, 2016
The effects of Staphylococcal enterotoxin B (SEB) on regulation of immune response have been recognized; whether SEB can enhance the effects of immunotherapy on glioma remains to be investigated. This study tests a hypothesis that administration with SEB enhances the effects of specific immunotherapy on glioma growth in mice. In this study, a glioma-bearing mouse model was developed by adoptive transfer with GL261 cells (a mouse glioma cell line). The mice were treated with the GL261 cell extracts (used as an Ag) with or without administration of SEB. We observed that treating glioma-bearing mice with the glioma Ag and SEB induced glioma-specific Th9 cells in both glioma tissue and the spleen. Treating CD4+ CD25− T cells with SEB increased p300 phosphorylation, histone H3K4 acetylation at the interleukin (IL)-9 promoter locus, and increased the IL-9 transcriptional factor binding to the IL-9 promoter. Treating CD4+ CD25− T cells with both SEB and glioma Ag induced glioma-specific Th9 cells. The glioma-specific Th9 cells induced glioma cell apoptosis in the culture. Treating the glioma-bearing mice with SEB and glioma Ag significantly inhibited the glioma growth. In conclusion, SEB plus glioma Ag immunotherapy inhibits the experimental glioma growth, which may be a novel therapeutic remedy for the treatment of glioma.
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