Abstract
In this study, we demonstrate that tumor-derived exosome-loaded dendritic cells can elicit a specific CD8+ cytotoxic T-lymphocyte (CTL) response against autologous tumor cells in patients with malignant glioma. Exosomes were purified by ultrafiltration centrifugation and sucrose gradient ultracentrifugation. Exosomes had antigen-presenting molecules (MHC-I, HSP70), tumor antigen (MAGE-1) and adherent molecule (ICAM-1). After incubation with exosomes, the dendritic cells (DCs) could activate the T lymphocytes to become glioma-specialized CTL. The CTL had vigorous cytotoxicity to glioma cells as opposed to autologous lymphoblast cells. These data demonstrate that tumor exosome-loaded DC can be an effective tool in inducing glioma-specific CD8+ CTLs able to kill autologous glioma cells in vitro. In conclusion, exosomes are a natural and new source of tumor-rejection antigens, opening up new avenues for immunization against glioma.
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Acknowledgments
This study was supported by the Xi’an Jiaotong University President’s Fund, no. xjj2008021. Contributions: Ning Bu obtained research funding, interpreted and analysed the data, and provided a draft of the article; Bingzhong Sun contributed to the concept and design, and provided critical revisions and important intellectual content; Shuqin Zhan, Ru Zhang, Le Zhou provided the study materials and administrative support; Haiqin Wu, Guilian Zhang, provided technical and logistical support.
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Bu, N., Wu, H., Sun, B. et al. Exosome-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with glioma. J Neurooncol 104, 659–667 (2011). https://doi.org/10.1007/s11060-011-0537-1
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DOI: https://doi.org/10.1007/s11060-011-0537-1