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树突状细胞与肝癌细胞融合物免疫小鼠对诱导的肝细胞癌(HCC)的预防性抗肿瘤活性。

Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice.

作者信息

Homma S, Toda G, Gong J, Kufe D, Ohno T

机构信息

Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.

出版信息

J Gastroenterol. 2001 Nov;36(11):764-71. doi: 10.1007/s005350170019.

Abstract

BACKGROUND

The prevention of recurrence of hepatocellular carcinoma (HCC) after treatment is very important for improvement of the prognosis of HCC patients. Dendritic cells (DCs) are potent antigen-presenting cells that can prime naive T cells to induce a primary immune response. We attempted to induce preventive antitumor immunity against HCC by immunizing BALB/c mice with fusions of DCs and HCC cells.

METHODS

Murine bone marrow-derived DCs and a murine HCC cell line. BNL cells, were fused by treatment with 50% polyethyleneglvcol (PEG). Fusion efficacy was assessed by the analysis of fusions of BNL cells stained with red fluorescent dye and DCs stained with green fluorescent dye. Mice injected intravenously with DC/BNL fusions were challenged by BNL cell inoculation.

RESULTS

About 30% of the PEG-treated non-adherent cells with both fluorescences were considered to be fusion cells. The cell fraction of DC/BNL fusions showed phenotypes of DCs, MHC class II, CD80, CD86, and intercellular adhesion molecule (ICAM)-1, which were not expressed on BNL cells. Mice immunized with the fusions were protected against the inoculation of BNL tumor cells, whereas injection with a mixture of DCs and BNL cells not treated with PEG did not provide significant resistance against BNL cell inoculation. Splenocytes from DC/BNL fusion-immunized mice showed lytic activity against BNL cells.

CONCLUSIONS

These results demonstrate that immunization with fusions of DCs and HCC cells is capable of inducing preventive antitumor immunity against HCC.

摘要

背景

肝细胞癌(HCC)治疗后预防复发对于改善HCC患者的预后非常重要。树突状细胞(DCs)是强大的抗原呈递细胞,可激活初始T细胞以诱导初次免疫反应。我们试图通过用DCs与HCC细胞的融合体免疫BALB/c小鼠来诱导针对HCC的预防性抗肿瘤免疫。

方法

用50%聚乙二醇(PEG)处理小鼠骨髓来源的DCs和小鼠HCC细胞系BNL细胞进行融合。通过分析用红色荧光染料染色的BNL细胞与用绿色荧光染料染色的DCs的融合情况来评估融合效率。静脉注射DC/BNL融合体的小鼠通过接种BNL细胞进行攻击。

结果

约30%经PEG处理的具有两种荧光的非贴壁细胞被认为是融合细胞。DC/BNL融合体的细胞部分表现出DCs、MHC II类、CD80、CD86和细胞间黏附分子(ICAM)-1的表型,这些在BNL细胞上未表达。用融合体免疫的小鼠对BNL肿瘤细胞的接种具有抵抗力,而注射未经PEG处理的DCs和BNL细胞的混合物对BNL细胞接种没有提供显著的抵抗力。来自DC/BNL融合体免疫小鼠的脾细胞对BNL细胞表现出裂解活性。

结论

这些结果表明,用DCs与HCC细胞的融合体免疫能够诱导针对HCC的预防性抗肿瘤免疫。

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