Hao Siguo, Bai Ou, Yuan Jinying, Qureshi Mabood, Xiang Jim
Research Unit, Division of Health Research, Saskatchewan Cancer Agency, Department of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada.
Cell Mol Immunol. 2006 Jun;3(3):205-11.
Exosomes (EXO) derived from dendritic cells (DC) and tumor cells have been used to stimulate antitumor immune responses in animal models and in clinical trials. However, there has been no side-by-side comparison of the stimulatory efficiency of the antitumor immune responses induced by these two commonly used EXO vaccines. In this study, we selected to study the phenotype characteristics of EXO derived from a transfected EG7 tumor cells expressing ovalbumin (OVA) and OVA-pulsed DC by flow cytometry. We compared the stimulatory effect in induction of OVA-specific immune responses between these two types of EXO. We found that OVA protein-pulsed DCOVA-derived EXO (EXODC) can more efficiently stimulate naïve OVA-specific CD8+ T cell proliferation and differentiation into cytotoxic T lymphocytes in vivo, and induce more efficient antitumor immunity than EG7 tumor cell-derived EXO (EXOEG7). In addition, we elucidated the important role of the host DC in EXO vaccines that the stimulatory effect of EXO is delivered to T cell responses by the host DC. Therefore, DC-derived EXO may represent a more effective EXO-based vaccine in induction of antitumor immunity.
源自树突状细胞(DC)和肿瘤细胞的外泌体(EXO)已被用于在动物模型和临床试验中刺激抗肿瘤免疫反应。然而,对于这两种常用的EXO疫苗诱导的抗肿瘤免疫反应的刺激效率,尚未进行过并列比较。在本研究中,我们选择通过流式细胞术研究源自表达卵清蛋白(OVA)的转染EG7肿瘤细胞和OVA脉冲DC的EXO的表型特征。我们比较了这两种类型的EXO在诱导OVA特异性免疫反应方面的刺激效果。我们发现,OVA蛋白脉冲的DC来源的EXO(EXODC)在体内能更有效地刺激初始OVA特异性CD8 + T细胞增殖并分化为细胞毒性T淋巴细胞,并且比EG7肿瘤细胞来源的EXO(EXOEG7)诱导更有效的抗肿瘤免疫。此外,我们阐明了宿主DC在EXO疫苗中的重要作用,即EXO的刺激作用通过宿主DC传递给T细胞反应。因此,DC来源的EXO在诱导抗肿瘤免疫方面可能代表一种更有效的基于EXO的疫苗。