B16F10/IL-21-gpi瘤苗通过减少调节性T细胞发挥治疗鼠黑色素瘤作用  

Treatment of murine melanoma with glycosyl phosphatidylinositol-anchored mIL-21 on B16F10 tumor vaccine B16F10/IL-21-gpi by the inhibition of the regulatory T cells in mice

作　　者：赵枫姝[1] 胡卫华[1] 窦骏[1] 胡凯[1] 何向锋[1] 唐权[1] 吴昀[1] 褚莉莉[1] 文萍[1] 刘春生[1] 

机构地区：[1]东南大学基础医学院病原生物学和免疫学系,南京210009

出　　处：《现代免疫学》2009年第2期100-105,共6页Current Immunology

基　　金：江苏省六大人才高峰项目(医药行业D14);国家自然基金资助项目(90406023)

摘　　要：观察B16F10/IL-21-gpi瘤苗对小鼠黑色素瘤治疗作用,并探讨其作用机制。以灭活的B16F10/IL-21-gpi瘤苗治疗黑色素瘤小鼠,经观察小鼠肿瘤生长大小、生存期长短判断其治疗肿瘤效应。以双抗夹心ELISA法检测小鼠脾细胞分泌的IL-4、IFN-γ和RT-PCR法检测肿瘤组织中IL-21的表达状况;同时以流式细胞仪检测小鼠脾细胞、肿瘤组织中和肿瘤引流淋巴结Treg的比例。结果显示,B16F10/IL-21-gpi瘤苗治疗鼠未成瘤率增高,肿瘤生长变慢;GPI锚定的IL-21瘤苗可很好地在肿瘤局部表达,Treg比例减少,脾细胞分泌的IFN-γ有明显地升高。该结果表明B16F10/IL-21-gpi瘤苗具有良好的治疗鼠黑色素瘤作用,并可能通过表达IL-21诱导IFN-γ分泌增加而抑制Treg细胞的减少达到抗肿瘤效应。The effect of treatment of murine melanoma with glycosyl phophatidylinositol （GPI）-anchored mlL-21 on B16F10 tumor vaccine B16F/IL-21-gpi was observed and its mechanism of action was investigated in the present study, in which the inactivated tumor vaccine was used to treat murine melanoma and the effect of treatment was evaluated by monitoring the tumor size and the survival time of tumor-bearing mice after the tumor vaccine was inoculated subcutaneously to C57BL mice. The IL- 4 and IFN-γ secreted in splenocytes and the expression of IL-21 in the tumor tissues were detected by ELISA and RT-PCR assay respectively. Meanwhile, the proportion of the regulatory T cells （Treg） in spenocytes, tumor tissues and the draining lymph nodes separately by flow cytometry （FCM）. In comparison with the tumor-free mice, the rate of tumor formation in mice inoculated with tumor vaccine B16F10/IL-21-gpi was reduced and the rate of tumor growth in mice with the developed tumor was slower. The GPI-anchored IL-21 tumor vaccine expressed well in the tumor tissues and the proportion of Treg was decreased with an increased proportion of IFN-γ secreted by the splenocytes compared with the control mice. These results indicate that tumor vaccine B16F10/IL-21-gpi has an excellent anti-tumor effect against murine melanoma in vitro through inhibition of the reduction in number of regulatory T cells by expression of IL-21 to induce an increased secretion of cytokine IFN-γ.

关 键 词：瘤苗 IL-21 TREG 

分 类 号：R392.12[医药卫生—免疫学]