Abstract
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.
Highlights
Glioma is a common malignant tumor in the brain, accounting for approximately 50% of primary brain tumors
The results suggest that the Ag/Staphylococcal enterotoxin B (SEB) immunotherapy induces IL-9 production in the glioma-bearing mice
Bonomi et al reported that human CD14+ cell-derived dendritic cells (DC) primed by Paclitaxel strongly inhibited proliferation of U87 MG cells [20]
Summary
Glioma is a common malignant tumor in the brain, accounting for approximately 50% of primary brain tumors. Despite rapid developments of surgical therapy, radiation therapy and chemotherapy in recent decades, the therapeutic effect on glioma is still poor [1]. Other additional anti-tumor strategies may be carried out to enhance the effects of surgical or/and radiological therapies for glioma. The discovery of cancer specific antigens (Ag), including exclusively or preferentially expressing in tumors, greatly potentiate the immunotherapy in cancer [3]. The major antitumor immune cells include T helper (Th) cells, Th2 cells, CD8+ cytotoxic T cells, natural killer (NK) cells and NKT cells, etc. These antitumor cells release cytokines to induce cancer cell death and inhibit cancer growth [4, 5]. The generation of Th9 cells in tumorbearing subjects is unclear
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