Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens.
Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens.
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DOI：
10.1002/stem.102
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Yu JS
中科院分区：
文献类型：
--
作者：
Xu Q;Liu G;Yuan X;Xu M;Wang H;Ji J;Konda B;Black KL;Yu JS
多形性胶质母细胞瘤是最具侵袭性的原发性脑肿瘤，目前的治疗仍然是姑息性的。免疫疗法利用人体自身的免疫系统来靶向癌症，可以克服传统治疗的局限性。一种主动免疫治疗策略使用基于树突状细胞（DC）的疫苗接种来启动T细胞介导的抗肿瘤免疫。已经提出癌症干细胞样细胞（CSCs）可能在癌症的发生、进展和对当前治疗的抗性中起关键作用。然而，使用人CSC抗原是否可以改善DC疫苗接种对人癌症的抗肿瘤作用尚不清楚。在本研究中，我们探索了CSC作为DC疫苗接种人GBM的抗原来源的适用性，目的是实现CSC靶向和增强抗肿瘤免疫。我们发现CSC表达高水平的肿瘤相关抗原（TAAs）以及主要组织相容性复合体（MHC）分子。此外，使用CSC抗原的DC疫苗接种引发针对CSC的抗原特异性T细胞应答。DC疫苗接种诱导的干扰素（IFN）-γ产生与产生的抗原特异性T细胞的数量正相关。最后，使用9 L CSC脑肿瘤模型，我们证明了用负载有9 L CSC的DC而不是子细胞或常规培养的9 L细胞接种，诱导了针对CSC的CTL，并延长了携带9 L CSC肿瘤的动物的存活。了解CSC免疫如何产生上级抗肿瘤免疫可能会加速CSC特异性免疫疗法和癌症疫苗的开发。
Glioblastoma multiforme is the most aggressive primary brain tumor, with current treatment remaining palliative. Immunotherapies harness the body’s own immune system to target cancers and could overcome the limitations of conventional treatments. One active immunotherapy strategy uses dendritic cell (DC)-based vaccination to initiate T cell-mediated anti-tumor immunity. It has been proposed that cancer stem-like cells (CSCs) may play a key role in cancer initiation, progression and resistance to current treatments. However, whether using human CSC antigens may improve the anti-tumor effect of DC vaccination against human cancer is unclear. In this study, we explored the suitability of CSCs as sources of antigens for DC vaccination again human GBM, with the aim of achieving CSC-targeting and enhanced anti-tumor immunity. We found that CSCs express high levels of tumor associated antigens (TAAs) as well as major histocompatibility complex (MHC) molecules. Furthermore, DC vaccination using CSC antigens elicited antigen-specific T cell responses against CSCs. DC vaccination induced interferon (IFN) -γ production is positively correlated with the number of antigen-specific T cells generated. Finally, using a 9L CSC brain tumor model, we demonstrate that vaccination with DCs loaded with 9L CSCs, but not daughter cells or conventionally cultured 9L cells, induced CTLs against CSCs, and prolonged survival in animals bearing 9L CSC tumors. Understanding how immunization with CSCs generates superior anti-tumor immunity may accelerate development of CSC-specific immunotherapies and cancer vaccines.
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