树突状细胞介导的肝癌免疫治疗实验研究

An experimental study on immunotherapy of liver cancer mediated by dendritic cells

目的探讨以树突状细胞(DC)为介导的原发性肝癌免疫治疗新方法。方法采用肝癌细胞制备肿瘤细胞性抗原冲击致敏体外培养的DC,体外混合淋巴细胞反应检测抗原致敏DC刺激同基因T淋巴细胞增殖的能力,观察负载肿瘤抗原的DC体内外诱导产生肿瘤特异性细胞毒T淋巴细胞(CTL)及其抗肿瘤能力。结果经肝癌细胞抗原致敏的DC能诱导较强的自体T细胞增殖,且能诱导特异性CTL,该CTL对自体肝癌细胞具有很强的杀伤活性,杀伤率明显高于DC和未经肝癌细胞抗原致敏的DC激活的CTL及T淋巴细胞的杀伤率,而对非同种肿瘤细胞无明显的杀伤作用,经BEL7402肿瘤细胞抗原致敏的DC经皮下免疫小鼠可诱导有效的免疫保护作用,可抵抗野生型BEL7402细胞的再攻击,肿瘤生长受到明显抑制,瘤体出现延迟,生长减慢。结论DC具有强大的刺激T淋巴细胞增殖和诱导产生特异性CTL的能力,在体内外均能激发特异性抗肿瘤免疫应答。

Objective To investigate the new immunotherapy of liver cancer which is mediated by decdritic cells （DC） .Methods DC was pulsed ex vivo by liver cancer ceils antigen. T ceils proliferation capability, cytotoxic T lymphocytes （CTL） and its anti-tumor capability was detected by mixed lymphocytes reaction. Results DC pulsed by hepatocellular carcinoma antigen could induce large amount of auto T cell proliferation and produce potent and specific anti-tumor action, and its kill rates was markedly higher than the control group and simple DC group. This CTL could not kill the heterogeneous tumor cells. An effective immunoprotection for mouse liver cancer could be induced by subcutaneous injection DC pulsed by BEL 7402 tumor antigen. These mice could effectively resist to the wild type BEL 7402, the tumor growth was obviously inhibited. Conclusion DC pulsed by auto-antigen has a potent capability of inducing T ceils proliferation and induce specific anti-tumor immune response in vivo or ex vivo.