MAGE-1抗原肽致敏DC活化淋巴细胞对裸鼠肝癌移植瘤的免疫防护作用

目的　观察黑色素瘤 1基因 (MAGE 1)抗原肽致敏树突状细胞 (DC)所活化的淋巴细胞(CTL)对人肝癌HCC移植瘤的抑制和消退作用 ,评估临床治疗HCC的可行性和有效性。　方法BEL 74 0 2HCC细胞于 30只裸鼠背部皮下接种 ,建立裸鼠HCC移植瘤模型 ,其中 2 2只成瘤 ;用MAGE 1九肽致敏DC所活化的淋巴细胞 (1× 10 6)注入肿瘤部位皮下 (治疗组A ,n =5 ) ,其余 17只随机分成 5组 (B、C、D、E、F) ,用其他不同性质的细胞治疗 ,观察各组肿瘤生长情况并进行病理学分析和统计学处理 ,阐明特异性CTL对肿瘤的作用机制。　结果　 (1)A组HCC移植瘤均停止生长并趋于缩小 ,荷瘤裸鼠观察期内无死亡 ;而其他 5组肿瘤均快速生长 ,大部分荷瘤裸鼠 2周内死亡。MAGE 1九肽致敏DC所活化淋巴细胞能显著抑制HCC移植瘤生长 ,促使肿瘤消退 (P <0 0 1)。 (2 )A组移植肿瘤广泛坏死 ,肿瘤细胞广泛凋亡。　结论　MAGE 1九肽致敏DC有抑制HCC生长 ,促进HCC消退 ,防止肿瘤转移、复发的作用。肿瘤细胞凋亡增强是DC肿瘤免疫的可能机制。MAGE 1九肽联合DC可作为治疗HCC的新型疫苗。

Inhibitory effect of dendritic cells induced activated cytotoxicity T lymphocyte combined with MAGE-1 nonapeptide on transplanted human hepatocyte carcinoma in nude mice

OBJECTIVE: To observe the inhibitory effect of dendritic cells (DCs) activated cytotoxicity T lymphocyte (CTL) combined with MAGE-1 nonapeptide on transplanted human hepatocyte carcinoma (HCC) in nude mice. METHODS: A model of HCC transplanted tumor was established by injecting BEL-7402 cell line HCC cells subcutaneously on the back of nude mice. Successful transplantation rate was 73%. Specific CTLs (1 x 10(6)), which were activated by DCs combined with MAGE-1 nonapeptide, were injected into the site of transplanted tumor (group A, n = 5). Another group of 17 mice were treated with same amounts of different kinds of cells, and they were divided into groups B, C, D, E, and F. The growth of tumor was observed, and pathological examination was also done. RESULTS: (1) The activated lymphocytes induced by DCs combined with MAGE-1 nonapeptide could suppress the growth of tumor and reduce the tumor size. In group A, 5/5 mice survived for at least two weeks, while the tumors grew rapidly and the majority of the mice died within two weeks in other groups (groups B, C, D, E, F) (P < 0.01). (2) Extensive necrosis and apoptosis were found in transplanted tumors in group A. CONCLUSIONS: The DCs combined with MAGE-1 nonapeptide could not only inhibit the growth of HCC, but also result in produce death and apoptosis of HCC, hence preventing tumor metastasis and recurrence. The mechanism underlying tumor immunization resulted from DCs might be enhanced in apoptosis of tumor cells. MAGE-1 nonapeptide combined with DCs might be a potential novel tumor vaccine for the treatment of HCC.