冻融抗原冲击致敏的树突状细胞诱导产生肺癌特异性免疫应答的实验研究  

An experimental study on induction of lung cancer specific immune response by vaccination of freeze-thaw cell lysate-pulsed dendritic cells

作　　者：才志刚[1] 段德溥[1] 张绍明[1] 吴胜勇[1] 肖海波[1] 周宜勇[1] 

机构地区：[1]解放军第455医院胸心外科,上海200052

出　　处：《南通大学学报（医学版）》2006年第5期321-324,共4页Journal of Nantong University(Medical sciences)

摘　　要：目的:利用树突状细胞递呈肿瘤抗原的特性提高细胞毒T淋巴细胞(CTLs)对肺癌细胞的杀伤活性。方法:外周血单个核细胞体外经GM-CSF和IL-4诱导产生树突状细胞,负载A549肺癌细胞裂解物的同时加入新型热休克蛋白(Hsp70L1),不同分组分别诱导自体CTLs产生。用细胞毒试验和ELISA测定CTLs杀伤活性和细胞因子的分泌。结果:A549冻融抗原致敏的DCs增加CTLs增殖,上调CTLs中CD3+和CD8+T细胞群及Th1型细胞因子的分泌;诱导的CTLs对A549细胞产生特异性杀伤;在加入Hsp70L1后效果更加明显。结论:DCs能有效呈递肺癌冻融抗原。诱导产生抗原特异性CTLs,加入免疫佐剂热休克蛋白后CTLs杀伤活性进一步增强。提示DCs在肺癌疫苗和过继免疫治疗中具有广阔的应用前景。Objective：To make use of the characteristics of presenting and processing tumor antigen of dendritic cells to enhance killing capability of CTL against lung cancer. Methods： Autologous dendritic cells were isolated from PBMC and then stimulated in vitro with granulocyte -macrophage colony -stimulating factor（ GM -CSF） and interleukin -4 （IL -4 ）. Dendritic cells were loaded with A549 tumor cell freeze - thaw lysate; at the same time Hsp70Ll as an immunol adjuvant was added. The specific groupings each induce generation of tumor specific cytotoxic T cells （ CTLs）. Killing activity and cytokine release of the CTL and the population of CTL were measured by cytotoxic assay and ELISA and FACS analyses. Results： DCs pulsed with A549 tumor cell lysate can enhance the growth expansion of CTL;up - regulation of the CD3 ＋ and CD8 ＋ population in CTL as well as an augmentation of Tbl eytokines; the eytotoxicity of specific CTL against A549 was highly enhanced; The above indications become more obvious after the addition of Hsp70L1. Conclusion：These results indicate that DCs can process and present tumor antigen to stimulate generation of specific CTL and with the addition of HspTOLl ,this activity can be further enhanced, It is suggested that DCs possess a clinically useful prospect of vaccines and specific CTL adoptive immunotherapy in patient with lung cancer.

关 键 词：肺肿瘤 T淋巴细胞 热休克蛋白 树突状细胞 肿瘤裂解物 

分 类 号：R734.2[医药卫生—肿瘤]