Wang Xian-Hua, Qin Yan, Hu Mei-Hao, Xie Yong
College of Life Sciences, Peking University, Beijing 100871, China.
World J Gastroenterol. 2005 Sep 28;11(36):5614-20. doi: 10.3748/wjg.v11.i36.5614.
To investigate the anti-tumor effect of dendritic cells (DCs) pulsed with hsp70-peptide complexes derived from human hepatocellular carcinoma (HCC) cells on human T cells.
Hsp70-peptide complexes were purified from human HCC cells with column chromatography using ADP-agarose and DEAE-Sepharose. DCs were derived from peripheral blood mononuclear cells of healthy donors in the presence of human GM-CSF and IL-4. The anti-tumor effect of DCs pulsed with hsp70-peptide complexes on human T-cell was assayed by CTL and enzyme-linked immunospot (ELISPOT) tests.
Hsp70-peptide complexes derived from human HCC cells activated phenotypic and functional maturation of DCs. The matured DCs stimulated a high level of autologous T-cell proliferation and type I cytokine secretion, and induced HCC-specific cytotoxic T lymphocytes (CTLs), which specifically killed HCC cells by a MHC class I restricted mechanism.
Hsp70-peptide complexes derived from human HCC cells can serve as a potent tumor antigen source for pulsing DCs, the pulsed DCs are very effective in activating specific T-cell responses against HCC cells.
研究用人肝癌(HCC)细胞来源的热休克蛋白70-肽复合物(hsp70-肽复合物)脉冲树突状细胞(DCs)对人T细胞的抗肿瘤作用。
使用ADP-琼脂糖和二乙氨基乙基琼脂糖通过柱色谱从人肝癌细胞中纯化hsp70-肽复合物。在人粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)存在的情况下,从健康供体的外周血单个核细胞中获得DCs。通过细胞毒性T淋巴细胞(CTL)和酶联免疫斑点(ELISPOT)试验检测用hsp70-肽复合物脉冲的DCs对人T细胞的抗肿瘤作用。
人肝癌细胞来源的hsp70-肽复合物激活了DCs的表型和功能成熟。成熟的DCs刺激高水平的自体T细胞增殖和I型细胞因子分泌,并诱导肝癌特异性细胞毒性T淋巴细胞(CTLs),其通过MHC I类限制机制特异性杀伤肝癌细胞。
人肝癌细胞来源的hsp70-肽复合物可作为脉冲DCs的有效肿瘤抗原来源,脉冲后的DCs在激活针对肝癌细胞的特异性T细胞反应方面非常有效。