Poly(I:C) enhanced anti-cervical cancer immunities induced by dendritic cells-derived exosomes

Poly(I:C) enhanced anti-cervical cancer immunities induced by dendritic cells-derived exosomes
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Poly(I:C) 增强树突状细胞衍生的外泌体诱导的抗宫颈癌免疫

DOI:
10.1016/j.ijbiomac.2018.02.034
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发表时间:
2018-07-01
影响因子:
8.2
通讯作者:
Xu, Yunsheng
Xu, Yunsheng
中科院分区:
化学1区
文献类型:
--
作者:
Chen, Shisheng;Lv, Mingfen;Xu, Yunsheng

文献摘要

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树突状细胞(DC)来源的外泌体(Dexo)已被证实能够在体外和体内诱导特异性抗肿瘤免疫应答。本研究的目的是评估抗原脉冲的Dexo作为一种新的疫苗接种平台在宫颈癌免疫治疗中的应用。通过来自Dexo免疫小鼠的CD 8(+)T细胞和脾细胞的细胞增殖、细胞因子分泌和效应子功能来评估不同Dexo的免疫原性特征。此外,在荷宫颈癌小鼠中进一步比较Dexo引起的抗肿瘤免疫。负载E7(49-57)肽的Dexo能有效诱导CD 8(+)T细胞对TC-1肿瘤细胞的体外杀伤活性,促进CD 8(+)T细胞的增殖和IFN-γ的分泌。此外,Dexo疫苗还能促进E7抗原诱导的小鼠脾细胞免疫应答。值得注意的是,poly(I:C)是负载抗原的Dexo介导的针对宫颈癌的保护性免疫应答的显著更有效的诱导剂,并且进一步通过Dexo(E7 + pIC)显著抑制肿瘤生长并提高荷瘤小鼠的存活率来证明。我们提供的证据表明,聚(I:C)显着增加了有效的抗肿瘤免疫诱导抗原脉冲Dexo改善宫颈癌。(C)2018爱思唯尔出版社
Dendritic cell (DC)-derived exosomes (Dexo) has been confirmed to be able to induce the specific anti-tumor immune response ex vivo and in vivo. Here, the aim of this study was to evaluate the application of the antigen pulsed Dexo as a new vaccination platform in immunotherapy for cervical cancer. The immunogenic profile of the different Dexo was assessed by the cell proliferation, cytokines secretion and effector functions of CD8(+) T cells and the splenocytes from Dexo-vaccinated mice. Furthermore, the anti-tumor immunity elicited by Dexo was further compared in cervical cancer-bearing mice. Dexo from DCs loaded with E7(49-57) peptide could efficiently induce the cytotoxic activity of CD8(+) T cells on TC-1 tumor cells ex vivo, the proliferation and IFN-gamma, excretion of CD8(+) T cells. Moreover, Dexo vaccine promoted the immune responses of vaccinated mice splenocytes induced by antigen E7 in vitro restimulation. Of note, poly(I:C) was significantly more potent inducer of the antigen-loaded Dexo mediated protective immunity responses for cervical cancer and further evidenced by that Dexo(E7 + pIC) markedly inhibited the tumor growth and improved the survival rate of the tumor-bearing mice. We provided evidence that poly(I:C) dramatically increased the potent antitumoral immunity induced by antigen-pulsed Dexo for ameliorating cervical cancer. (C) 2018 Published by Elsevier B.V.