Cancer stem cell vaccination confers significant antitumor immunity.
Cancer stem cell vaccination confers significant antitumor immunity.
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DOI：
10.1158/0008-5472.can-11-1400
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发表时间：
2012-04-01
期刊：
影响因子：
11.2
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Ning N;Pan Q;Zheng F;Teitz-Tennenbaum S;Egenti M;Yet J;Li M;Ginestier C;Wicha MS;Moyer JS;Prince ME;Xu Y;Zhang XL;Huang S;Chang AE;Li Q
大多数癌症干细胞（CSC）的研究涉及将来自人类肿瘤的细胞接种到免疫抑制小鼠中，从而阻止了对CSC的免疫相互作用和影响的评估。在这项研究中，我们研究了CSC富集的群体从组织学上不同的小鼠肿瘤接种到不同的同基因免疫活性宿主后产生的疫苗接种效果。富集的CSC具有免疫原性，并且在诱导保护性抗肿瘤免疫方面，富集的CSC作为抗原来源比肿瘤细胞更有效。来自接种CSC的宿主的免疫血清含有高水平的IgG，其与癌症干细胞结合，导致在补体存在下CSC裂解。从接种CSC的宿主收获的PBMC或脾细胞产生的CTL能够在体外杀死CSC。机制研究确定CSC引发的抗体和T细胞能够选择性靶向CSC并赋予抗肿瘤免疫。总之，这些概念验证结果为基于可以特异性靶向CSC的CSC疫苗的开发的新型癌症免疫疗法提供了理论基础。
Most studies of cancer stem cells (CSC) involve the inoculation of cells from human tumors into immunosuppressed mice, preventing an assessment on the immunological interactions and effects of CSCs. In this study, we examined the vaccination effects produced by CSC-enriched populations from histologically distinct murine tumors after their inoculation into different syngeneic immunocompetent hosts. Enriched CSCs were immunogenic and more effective as an antigen source compared with unselected tumor cells in inducing protective anti-tumor immunity. Immune sera from CSC-vaccinated hosts contained high levels of IgG which bound to cancer stem cells, resulting in CSC lysis in the presence of complement. CTLs generated from PBMCs or splenocytes harvested from CSC-vaccinated hosts were capable of killing CSCs in vitro. Mechanistic investigations established that CSC-primed antibodies and T cells were capable of selective targeting CSCs and conferring anti-tumor immunity. Together, these proof of concept results provide a rationale for a new type of cancer immunotherapy based on the development of CSC vaccines that can specifically target CSCs.