Combined radiation therapy and dendritic cell vaccine for treating solid tumors with liver micro-metastasis
Combined radiation therapy and dendritic cell vaccine for treating solid tumors with liver micro-metastasis
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DOI：
10.1002/jgm.692
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发表时间：
2005-04-01
影响因子：
3.5
通讯作者：
Xiang, J
中科院分区：
文献类型：
--
作者：
Chen, Z;Xia, DJ;Xiang, J
背景肿瘤转移和复发是人类恶性肿瘤防治的主要障碍。无论是单纯的放射治疗还是树突状细胞（DC）的注射都不能成功地克服这个问题。放射线可诱导肿瘤细胞凋亡和坏死，导致肿瘤抗原和危险信号的释放，有利于DC捕获抗原并成熟。方法采用皮下注射（s.c.）和静脉内（i.v.）注射结果放疗联合DC瘤内注射能诱导机体产生较强的抗肿瘤免疫应答，显著降低肿瘤局部复发率和肝转移灶数目。其机制可能与照射后产生凋亡坏死肿瘤抗原和热休克蛋白、DCs的吞噬、迁移和成熟有关，并通过交叉呈递途径诱导更有效的肿瘤特异性细胞毒性T淋巴细胞活性。局部照射和瘤内注射DC可能是临床治疗放射敏感性肿瘤和消除转移的有希望的策略。版权所有（c）2004年约翰威利父子有限公司。
Background Tumor metastasis and relapse are major obstacles in combating human malignant diseases. Neither radiotherapy alone nor injection of dendritic cells (DCs) can successfully overcome this problem. Radiation induces tumor cell apoptosis and necrosis, resulting in the release of tumor antigen and danger signals, which are favorable for DC capturing antigens and maturation. Hence, the strategy of combined irradiation and DC vaccine may be a novel approach for treating human malignancies and early metastasis.Methods To develop an effective combined therapeutic approach, we established a novel concomitant local tumor and liver metastases model through subcutaneous (s.c.) and intravenous (i.v.) injection. We selected the optimal time for DC injection after irradiation and investigated the antitumor effect of combining irradiation with DC intratumoral injection and the related mechanism.Results Combined treatment with radiotherapy and DC vaccine could induce a potent antitumor immune response, resulting in a significant decrease in the rate of local tumor relapse and the numbers of liver metastases. The related mechanisms for this strong antitumor immunity of this combined therapy might be associated with the production of apoptotic and necrotic tumor antigens and heat shock proteins after irradiation, phagocytosis, migration and maturation of DCs, and induction of more efficient tumor-specific cytotoxic T lymphocyte activity through a cross-presentation pathway.Conclusions Co-administration of local irradiation and intratumoral DC injection may be a promising strategy for treating radiosensitive tumors and eliminating metastasis in the clinic. Copyright (c) 2004 John Wiley & Sons, Ltd.