半相合基因DCs-CTL对小鼠黑色素瘤的抑制作用及GVHD反应  

Adoptive transfer of haploidentical dentritic cell activated cytotoxic Tlymphocytes inhibits melanoma growth but does not induce significant graft-versushost reaction in tumor-bearing mice

作　　者：李冬斌[1] 司洪涛[1] 郑志刚[2] 茹丽娜 许香梅[3] 徐晓云[4] 蔡建辉[5] 

机构地区：[1]河北医科大学第二医院胃肠外科,河北省石家庄市050000 [2]石家庄市第一医院外一科,河北省石家庄市050010 [3]石家庄市第一医院心二科,河北省石家庄市050010 [4]河北医科大学第二医院消化内科,河北省石家庄市050010 [5]河北省人民医院普外科,河北省石家庄市050000

出　　处：《世界华人消化杂志》2015年第3期415-420,共6页World Chinese Journal of Digestology

摘　　要：目的:探讨半相合基因来源肿瘤特异性树突状细胞活化的特异性细胞毒性T淋巴细胞(the special cytotoxic T lymphocytes activated by dendritic cells,DCs-CTLs)体外静脉注射荷瘤鼠后观察其抑瘤效果及其移植物抗宿主反应(graft-versus-host disease,GVHD)的程度.方法:将B16黑色素瘤体外种植于健康C57BL/6小鼠成功后,全部在第10天给予60CO 7 Gy全身照射.将荷瘤小鼠随机分为阴性对照、自体治疗及半相合治疗组,分别于第10、17天给予小鼠自体红细胞、自体来源DCs-CTLs效应细胞、半相合鼠来源DCs-CTLs细胞经尾静脉注射治疗后,行GVHD评分;治疗后处死小鼠,取脾脏、肾和皮肤行病理检查,观察有无移植物抗宿主反应表现,并绘制肿瘤生长曲线、计算抑瘤率.结果:(1)3组GVHD反应评分结果:阴性对照组与自体治疗组、半相合治疗组相比差异均有统计学意义(P<0.05);自体治疗组与半相合治疗组之间比较无统计学意义,分别取3组小鼠的脾脏、皮肤和肾脏行病理检查,各组均未见明显移植物抗宿主反应的病理变化;(2)肿瘤生长曲线显示,自体治疗组和半相合治疗组均能明显抑制肿瘤生长,而阴性对照组对肿瘤的生长无明显抑制作用.自体治疗组和半相合基因治疗组瘤质量均低于阴性对照组,差异有统计学意义(P<0.05);自体治疗组和半相合基因治疗组之间瘤质量对比差异无统计学意义(P>0.05);自体治疗组和半相合治疗组抑瘤率对比差异无统计学意义(P>0.05).结论:自体治疗组及半相合基因治疗组均有明显抑瘤作用,治疗后观察半相合基因治疗组未见明显移植物抗宿主反应.AIM： To investigate the effect of haploidentical dentritic cell activated cytotoxic T lymphocytes（DC-CTCs） on melanoma growth in tumorbearing mice and whether DC-CTCs induce significant graft-versus-host reaction（GVHD）. METHODS： Thirty healthy C57BL/6 mice were used for implantation of B16 melanoma. Tumor-bearing mice were randomly divided into a negative control group, an autologous DC-CTLs group and a haploidentical DC-CTLs group. All rats were irradiated with 7 Gy 60 CO on day 10. The negative control group was intravenously given autologous erythrocytes via the tail vein on days 10 and 17; the autologous DC-CTLs group was given autologous DCCTLs; and the haploidentical DC-CTLs group was given haploidentical DC- CTLs. After treatment, GVHD was assessed, and tumor growth curve was plotted to calculate tumor inhibition rate.RESULTS： GVHD score differed significantly between the control group and autologous/haploidentical treatment groups（P〈 0.05）, while the two treatment showed no significant difference（P〉 0.05）. Pathological analysis of skin, spleen and kidney samples showed that there were no obvious pathological changes suggestive of GVHD in the three groups. Tumor growth curve analysis showed that tumor growth was significantly inhibited in the two treatment groups（P〈 0.05）, although no tumor growth inhibition was observed in the control group. Tumor growth inhibition was similar between the autologous treatment group and haploidentical treatment group.CONCLUSION： Autologous and haploidentical DC-CTLs show significant anti-tumor effects, and haploidentical DC-CTLs donot cause significant GVHD.

关 键 词：免疫治疗 半相合基因 移植物抗宿主反应 细胞毒性T淋巴细胞 

分 类 号：R730.51[医药卫生—肿瘤]