可溶性PD-1协同HSP70-肽复合物抑制荷瘤小鼠肝癌的研究  

Soluble PD-1 can augment anti-tumor immunity induced by HSP70-peptide complex in tumor-bearing mice

作　　者：王小红[1] 张桂梅[1] 贺宇飞[1] 张慧[1] 冯作化[1] 

机构地区：[1]华中科技大学同济医学院生物化学与分子生物学系,湖北武汉430030

出　　处：《细胞与分子免疫学杂志》2004年第6期655-658,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家重点基础研究发展规划(973)基金资助 (No .2 0 0 2CB51 31 0 0 )

摘　　要：目的 :研究基因转染和表达的可溶性PD 1(solubleprogrammeddeath 1,sPD 1)对HSP70 肽疫苗抗肿瘤效果的影响及协同机制。方法 :以HSP70 肽疫苗免疫BALB/c小鼠后 ,用半定量RT PCR技术检测和分析HSP70 肽疫苗对小鼠脾细胞上PD 1及其配体基因表达的影响。体内转染表达sPD 1,用MTT比色法检测HSP70 肽疫苗免疫小鼠对肿瘤生长的抑制作用以及脾淋巴细胞的细胞毒活性。结果 :单独的sPD 1就有抗肿瘤效应。HSP70 肽疫苗不仅能预先在动物体内诱导肿瘤特异性的CTL ,而且可使脾细胞上抑制性共刺激受体PD 1及其配体的表达显著升高。用sPD 1与HSP70 肽疫苗联合治疗荷瘤小鼠 ,能提高脾CTL的杀伤效率并延长HSP70 肽疫苗的免疫效果。结论 :sPD 1可通过阻断PD 1与其配体的结合作用 ,及减弱PD 1的负反馈抑制作用 ,而增强HSP70AIM: To explore the effect of soluble PD-1 (sPD-1) on the anti-tumor immunity induced by HSP70-peptide. METHODS: BALB/c mice were immunized with HSP70-peptide, then the cytotoxic activity of splenocytes was detected by MTT colorimetry. Expression of PD-1 and its ligand on splenocytes was determined by semi-quantitative RT-PCR. For some mice, sPD-1 plasmid was injected alone or in combination with HSP70-peptide and then the tumor’s weight and cytotoxic activity of splenocytes were measured. RESULTS: sPD-1 alone had anti-tumor effect. HSP70-peptide complex not only induced tumor-specific cytotoxic T lymphocytes(CTLs), but also promoted expression of PD-1 and its ligand. The combination of sPD-1 with HSP70-peptide complex induced much more stronger anti-tumor effect as compared with sPD-1 or HSP70-peptide alone. sPD-1 transfection in mice could enhance the cytotoxic activity of splenocytes from immunized mice. CONCLUSION: sPD-1 enhanced the anti-tumor efficacy of HSP70-peptide.

关 键 词：共刺激分子 PD-1 B7-H1 HSP70-肽复合物 

分 类 号：R733.6[医药卫生—肿瘤]