子宫颈癌患者树突状细胞体内外诱导抗肿瘤免疫

目的探讨子宫颈癌患者的树突状细胞(dendritic cells,DCs)在体内外能否诱导出高效而特异的抗肿瘤免疫应答。方法应用粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白介素-4(IL-4)从子宫颈癌患者外周血诱导DCs,Hela子宫颈癌抗原致敏,MTT法检测DCs激活的细胞毒性T淋巴细胞(CTLs)对肿瘤细胞的细胞毒作用。皮下接种Hela子宫颈癌建立荷瘤鼠,给予抗原致敏的DCs回输;或先给予DCs免疫,后用癌细胞攻击,观察其抑制肿瘤的效果。结果从子宫颈癌患者外周血诱导的DCs高表达CD86、CD12、HLA-DR、CD54和CD83,激活的CTLs在体外特异性杀伤子宫颈癌细胞。DCs回输小鼠具有免疫保护作用,减低成瘤率;又能引起免疫治疗作用,有效抑制肿瘤的生长。结论用GM-CSF及IL-4从子宫颈癌患者诱导的DCs能有效提呈Hela子宫颈癌抗原给T淋巴细胞,并且在体内外诱导出高效而特异的抗肿瘤免疫,有望成为有效的肿瘤特异性免疫治疗新途径。

Antitumor Immunity of Dendritic Cells Induced in Vitro and in Vivo in Patients with Carcinoma Cervicis

Objective To investigate whether dendritic cells(DCs) obtained from patients with carcinoma cervicis can be induced a efficient and specific immune response against carcinoma cervicis in vitro and in vivo.Methods Cocultured with combination of granulocyte/macrophage colony stimulating factors(GM-CSF) and interleukin 4(IL-4),DCs can be obtained from peripheral blood of patients with carcinoma cervicis.After activated with Hela-tumor-associated antigen(TAA),DCs were incubated with T lymphocytes to produce cytotoxic T lymphocytes(CTLs) and then the cytotoxic effect of CTLs on cancer cells was detested by MTT assay.The tumor mice were set up by incubation of Hela cells subcutaneously,then the antigen-activated DCs were given;or DCs were first given and then incubation of Hela cells was conducted.The immunotherapeutic effect to tumor was observed in vivo.Results DCs,induced from peripheral blood of patients with carcinoma cervicis,had a high expression of CD86,CD 40,HLA-DR,CD54 and CD83.The CTLs activated by DCs could specifically kill the cancer cells in vitro.Transfusion of DCs could immunologically protect the mice,reduce the rate of tumor formation,and prolong the latent period.Besides,it also could play an immunotherapeutic effect,and effectively inhibit the growth of tumor.Conclusion DCs,activated with GM-CSF and IL-4,can efficiently present antigen and induce effective immunoresponse to tumor.It will probably become an effective and special immunotherapy for antitumor.