自体宫颈癌-树突细胞疫苗激活的CTL杀伤效应  

Killing Activity of Cytotoxic T Lymphocytes Stimulated by Dendritic Cell Vaccine Loaded with Autologous Cervical Cancer Antigen

作　　者：周昌菊[1] 马薇[1] 周建大[2] 赵永祥[3] 谢慧清[4] 

机构地区：[1]中南大学湘雅三医院妇产科,湖南长沙410013 [2]中南大学湘雅三医院整形烧伤科,湖南长沙410013 [3]中南大学湘雅三医院医学移植中心,湖南长沙410013 [4]中南大学湘雅三医院康复医学科,湖南长沙410013

出　　处：《癌症》2006年第2期143-147,共5页Chinese Journal of Cancer

基　　金：湖南省自然科学基金(No.01JJY2086)~~

摘　　要：背景与目的:树突细胞(dendriticcells,DC)是目前已知的功能最强的抗原递呈细胞(antigen-presentingcell,APC),它可以在体内、外向T淋巴细胞递呈抗原,并诱发细胞毒T淋巴细胞(cytotoxicTlymphocyte,CTL)反应。本研究旨在探讨负载自体宫颈癌抗原的DC体外激发的CTL对自体宫颈癌细胞的杀伤效应。方法:先冻融宫颈癌细胞制备抗原,然后以GM-CSF、IL-4诱导自体外周血单个核细胞(peripheralbloodmononuclearcell,PBMC)获得DC并负载抗原,刺激自体T淋巴细胞制备宫颈癌抗原特异性CTL,观察CTL对宫颈癌细胞的杀伤活性。结果:负载自体宫颈癌抗原DC诱导的特异性CTL对自体宫颈癌细胞的体外杀伤率高达79.32%～89.27%,显著高于淋巴因子激活的杀伤细胞(lymphokine-activatedkillingcells,LAK)的杀伤率(t≥2.89,P<0.05);且对宫颈癌HeLa细胞株具有一定杀伤效应(40.35%～58.09%),但低于自体癌细胞组(t≥2.97,P<0.05);特异性CTL对HepG2、MCF7、A549、MGC803细胞无明显杀伤效应。结论:自体宫颈癌-树突细胞疫苗体外诱导的CTL具有高效而特异的抗自体宫颈癌细胞免疫活性,可望成为宫颈癌生物治疗的一个有力手段。BACKGROUND ＆ OBJECTIVE： Dendritic cells （DCs）, the strongest antigen-presenting cells （APCs）, can present antigens to T lymphocytes in vivo and in vitro, and induce cytotoxic T lymphocyte （CTL） reaction. This study was designed to investigate the killing activity of CTLs stimulated by Dcs loaded with autologous cervical cancer antigen in vitro. METHODS： Tumor antigens were made from frozen-thawed cervical cancer cells from patients after operation. DCs were isolated from peripheral blood mononuclear cells of patients with cervical cancer, cultured with granulocytemacrophage colony-stimulating factor （GM-CSF） and interleukin-4 （IL-4）, loaded with tumor antigen to prepare DC vaccine, and used to stimulate autologous T lymphocytes to prepare antigen-specific CTLs. The killing activities of CTLs on autologous cervical cancer cells and HeLa, HepG2, MCFT, A549, and MGC803 cells were observed. RESULTS： CTLs stimulated by the DC vaccine had high killing activity on autologous cervical cancer cells, with killing rates of 79.32%-89.27% which were obviously higher than that of lymphokine-activated killing cells （t≥2.89, P〈0.05）. The killing activity of CTLs was significantly weaker on HeLa cells （40.35%-58.09%） than on autologous cervical cancer cells （t≥2.97, P〈0.05）. The specific CTLs had no obvious killing activity on HepG2, MCFT, A549, and MGC803 cells. CONCLUSIONS： CTLs stimulated by autologous cervical cancer antigenloaded DCs have highly efficient and specific immune activity on autologous cervical cancer cells. It may be used in biotherapy for cervical cancer.

关 键 词：宫颈肿瘤 树突细胞 细胞毒性淋巴细胞 杀伤活性 

分 类 号：R737.33[医药卫生—肿瘤]