Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model.
Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model.
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DOI：
10.1186/1471-2407-7-87
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发表时间：
2007-05-23
期刊：
影响因子：
3.8
通讯作者：
Kim SJ
中科院分区：
文献类型：
--
作者：
Chang CY;Lee J;Kim EY;Park HJ;Kwon CH;Joh JW;Kim SJ
新型细胞因子白细胞介素（IL）-18是一种强干扰素-γ诱导剂和Th 1细胞活化中的共刺激因子。IL-18触发IFN-γ产生并增强T细胞和NK细胞中的细胞溶解活性。然而，IL-18抗肿瘤作用的确切机制仍有待澄清。为探讨IL-18质粒DNA对小鼠肝癌的治疗作用，在小鼠肝脏中建立了小鼠结肠癌细胞系CT 26。在肿瘤注射后7天将编码IL-18的质粒载体直接转移到肝脏中以限制肿瘤部位内的IL-18表达。IL-18蛋白水平在质粒注射后4天在肝脏中增加，并且在第7天观察到显著的抗肿瘤作用。通过测量肿瘤消退、免疫细胞群和IFN-γ产生来评价抗肿瘤作用。IL-18质粒控制肝肿瘤的生长和脾免疫细胞的增殖。此外，用IL-18质粒治疗CT 26肿瘤显著增强了脾和外周血中效应T和NK细胞的群体。在脾脏中，在第7天，响应于IL-18，CD 4 + CD 62低细胞群体增加。这些结果与分泌IFN-γ的CD 4 + T细胞而非CD 8 + T细胞的增加一致。荷瘤小鼠中肿瘤生长的显著减少与脾中响应于IL-18的IFN-γ产生的维持相关。这些抗肿瘤作用维持到质粒注射后14天。我们的研究结果表明，直接质粒DNA转移IL-18没有伴随试剂，以提高转染效率可能是有用的肿瘤免疫治疗。
The novel cytokine, interleukin (IL)-18, is a strong interferon-γ inducer and costimulatory factor in Th1 cell activation. IL-18 triggers IFN-γ production and enhances cytolytic activity in both T and NK cells. However, the exact mechanism of antitumor action of IL-18 remains to be clarified. To determine the effects of IL-18 plasmid DNA on hepatic cancer in mice, CT26 murine colon adenocarcinoma cells were established in mouse liver. Plasmid vectors encoding IL-18 were transferred directly into the liver 7 days after tumor injection to restrict IL-18 expression within the tumor site. The IL-18 protein level was increased in the liver 4 days after plasmid injection, and a marked antitumoral effect was observed at day 7. Antitumor effects were evaluated by measuring tumor regression, immune cell population, and IFN-γ production. The IL-18 plasmid controlled the growth of hepatic tumors and proliferation of splenic immune cells. Moreover, treatment of CT26 tumors with the IL-18 plasmid significantly enhanced the population of the effector T and NK cells in the spleen and peripheral blood. In spleen, the population of CD4+CD62Low cells was augmented in response to IL-18 on day 7. These results are consistent with the increase in CD4+ T cells secreting IFN-γ, but not CD8+ T cells. The marked reduction of tumor growth in tumor-bearing mice was associated with the maintenance of IFN-γ production in spleen in response to IL-18. These antitumoral effects were maintained until 14 days after plasmid injection. Our results suggest that direct plasmid DNA transfer of IL-18 with no accompanying reagents to augment transfection efficiency may be useful in tumor immunotherapy.