Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells.
Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells.
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基于树突状细胞的免疫疗法在 CD105 人肾癌干细胞中激发有效的抗肿瘤免疫反应
DOI：
10.1002/mc.22697
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Xia Jian-Chuan
中科院分区：
文献类型：
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作者：
Zhang Xiao-Fei;Weng De-Sheng;Pan Ke;Zhou Zi-Qi;Pan Qiu-Zhong;Zhao Jing-Jing;Tang Yan;Jiang Shan-Shan;Chen Chang-Long;Li Yong-Qiang;Zhang Hong-Xia;Chang Alfred E;Wicha Max S;Zeng Yi-Xin;Li Qiao;Xia Jian-Chuan
肿瘤干细胞（CSCs）负责肿瘤的发生、发展和对治疗药物的耐药性；它们通常对传统的癌症治疗不太敏感，并且可能导致肿瘤复发。因此，理想的治疗策略是选择性地靶向和破坏CSCs，从而防止肿瘤复发。本研究的目的是评估CD105+人肾细胞癌（RCC） CSCs衍生抗原脉冲树突状细胞（DCs）在体外和体内对肾癌细胞的作用。我们在两种人类RCC细胞系A498和SK‐RC‐39中发现了CD105+细胞的“干细胞样”特征。细胞裂解物的加载没有改变DCs的特性。然而，负载CD105+ CSCs裂解物的dc诱导了功能更特异的活性T细胞和针对CSCs的特异性抗体，并明显抑制了小鼠的肿瘤生长。我们的结果可以为一种新的策略奠定基础，以提高基于DC的人类RCC免疫治疗的疗效。
Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified “stem‐like” characteristics of CD105+ cells in two human RCC cell lines: A498 and SK‐RC‐39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC‐based immunotherapy for human RCC.