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目的:通过选择性增强树突状细胞(DC)与T细胞的体内相互作用,优化其体内抗原提呈的微环境,为进一步增强DC介导的肿瘤免疫治疗效果。方法:体外培养的小鼠骨髓树突状细胞体外经Ltn重组腺病毒感染后(Ltn-DC),用3LLLewis肺癌细胞株的Mutl抗原肽冲击致敏,按不同剂量免疫正常同系小鼠体内,观察其体内诱导的细胞毒性T淋巴细胞(CTL)活性保护性免疫反应;通过体内阻断试验探讨免疫细胞亚群及免疫分子在DC诱导肮肿瘤免疫应答中的作用;建立肺癌的自发性肺转移模型,观察免疫治疗作用。结果:抗原肽Mutl刺激的Ltn-DC能更有效地诱导特异CTL活性,能使免疫动物产生更有效的免疫保护作用,抵抗肿瘤细胞的攻击。在抗肿瘤免疫排斥反应的诱导过程中,必需有CD4+T和CD8+T细胞的参与;而在其效应阶段,则依赖于CD8+T细胞、B7/CD28的共刺激信号途径及γ干扰素(IFN-γ)的参与,并在诱导过程中起着重要作用。抗原肽刺激的Ltn-DC能有效抑制3LL细胞的自发性肺转移,具有更明显的治疗作用。结论:通过基因修饰增强树突状细胞对T细胞的体内选择性趋化活性,能更有效地诱导抗肿瘤免疫反应,为树突状细胞介导的肿瘤免疫治疗开辟了?
OBJECTIVE: To optimize the in vivo antigen presentation microenvironment by selectively enhancing the in vivo interaction between dendritic cells (DCs) and T cells, and to further enhance the efficacy of DC-mediated tumor immunotherapy. METHODS: Mice bone marrow dendritic cells cultured in vitro were infected with Ltn recombinant adenovirus (Ltn-DC) and challenged with Mutl antigen peptide of 3LL Lewis lung cancer cell line. The mice were immunized with different doses in normal syngeneic mice. Its in vivo induced cytotoxic T lymphocyte (CTL) activity protective immune response; The role of immune cell subpopulations and immune molecules in DC-induced immune response of solid tumors was investigated through in vivo blocking assays; Spontaneous lung metastasis model for lung cancer was established , observe the effect of immunotherapy. RESULTS: Ltn-DC stimulated by antigenic peptide Mutl was more effective in inducing specific CTL activity, which could make immune animals produce more effective immune protection against tumor cell attack. In the process of induction of anti-tumor immune rejection, there must be participation of CD4+T and CD8+ T cells; in its effect phase, it depends on CD8+ T cells, B7/CD28 costimulatory signal pathway and IFN-γ Participate and play an important role in the induction process. Ltn-DC stimulated by antigenic peptide can effectively inhibit the spontaneous lung metastasis of 3LL cells, and has a more obvious therapeutic effect. Conclusion: Through gene modification, the selective chemotactic activity of dendritic cells on T cells in vivo can be more effective in inducing anti-tumor immune responses and opening up for dendritic cell-mediated tumor immunotherapy.