Exosome-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with glioma

Exosome-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with glioma
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DOI:
10.1007/s11060-011-0537-1
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发表时间:
2011-09-01
影响因子:
3.9
通讯作者:
Zhou, Le
Zhou, Le
中科院分区:
医学2区
文献类型:
--
作者:
Bu, Ning;Wu, Haiqin;Zhou, Le

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在这项研究中,我们证明了肿瘤来源的装载外泌体的树突状细胞可以引起针对恶性胶质瘤患者自身肿瘤细胞的特异性CD8(+)细胞毒性t淋巴细胞(CTL)反应。外泌体通过超滤离心和蔗糖梯度超离心纯化。外泌体含有抗原提呈分子(mhc -1、HSP70)、肿瘤抗原(MAGE-1)和粘附分子(ICAM-1)。树突状细胞与外泌体孵卵后,可激活T淋巴细胞成为胶质瘤特化CTL。与自体淋巴母细胞相反,CTL对胶质瘤细胞具有强烈的细胞毒性。这些数据表明,负载肿瘤外泌体的DC可以是诱导能够在体外杀死自体胶质瘤细胞的胶质瘤特异性CD8(+) ctl的有效工具。总之,外泌体是一种天然的肿瘤排斥抗原的新来源,为免疫治疗胶质瘤开辟了新的途径。
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.