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肿瘤细胞衍生的外泌体靶向树突状细胞可刺激更强的 CD8+ CTL 反应和抗肿瘤免疫。

Tumor cell-derived exosome-targeted dendritic cells stimulate stronger CD8+ CTL responses and antitumor immunities.

机构信息

Department of Hematology, Xinhua Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Biochem Biophys Res Commun. 2013 Jun 21;436(1):60-5. doi: 10.1016/j.bbrc.2013.05.058. Epub 2013 May 22.

Abstract

Tumor cell-derived exosomes (TEX) have been widely used to induce antitumor immune responses in animal models and clinical trials. However, the efficiency of the antitumor immunity that is induced by TEX is still relatively weak. In this study, we compared the antitumor immunities between EG7 tumor cell-derived exosomes (EXO(EG7)) and EXO(EG7)-targeted dendritic cells (DC(EXO)). We found that EXO(EG7) harbored OVA and peptide major histocompatibility complex I (pMHC-I), which were expressed on its parental EG7 tmor cells, and they could transfer OVA and pMHC-I to dendritic cells (DCs) in vitro. DC(EXO) could more efficiently induce antitumor immunity than EXO(EG7). In addition, we showed that the immune stimulatory effects of EXO(EG7) were dependent on the host DCs and, whereas those of DC(EXO) were not, indicating the important role of the host DCs in TEX vaccines. Taken together, TEX-targeted DCs may be more effective for EXO-based vaccines for the induction of antitumor immunity.

摘要

肿瘤细胞衍生的外泌体 (TEX) 已被广泛用于在动物模型和临床试验中诱导抗肿瘤免疫反应。然而,TEX 诱导的抗肿瘤免疫的效率仍然相对较弱。在本研究中,我们比较了 EG7 肿瘤细胞衍生的外泌体 (EXO(EG7)) 和靶向 EXO(EG7) 的树突状细胞 (DC(EXO)) 之间的抗肿瘤免疫。我们发现 EXO(EG7) 携带 OVA 和肽主要组织相容性复合物 I (pMHC-I),这两种物质在其亲本 EG7 肿瘤细胞上表达,并且它们可以将 OVA 和 pMHC-I 转染到体外的树突状细胞 (DC) 中。DC(EXO) 比 EXO(EG7) 更有效地诱导抗肿瘤免疫。此外,我们表明 EXO(EG7) 的免疫刺激作用依赖于宿主 DC,而 DC(EXO) 的免疫刺激作用则不依赖于宿主 DC,这表明宿主 DC 在 TEX 疫苗中起着重要作用。综上所述,靶向 DC 的 TEX 可能更有利于基于外泌体的疫苗诱导抗肿瘤免疫。

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