趋化因子SLC和免疫佐剂CpG-ODN联合应用对小鼠移植黑素瘤的疗效  

Therapeutic effect of chemokine SLC combined with immune adjuvant CpG-ODN in treatment of implanted mouse melanoma

作　　者：许相范[1] 许振柱[2] 唐丽华[1] 李安娜[3] 徐显辉[1] 柳春宝[1] 

机构地区：[1]厦门市第二医院病理科,福建厦门361021 [2]厦门市第二医院检验科,福建厦门361021 [3]厦门市第二医院呼吸科,福建厦门361021

出　　处：《中国肿瘤生物治疗杂志》2010年第1期25-29,共5页Chinese Journal of Cancer Biotherapy

基　　金：厦门市科技局计划指导性项目(No.3502z20089020)~~

摘　　要：目的:探讨次级淋巴组织趋化因子(seccondary lymphoid tissue chemokine,SLC)和CpG寡聚脱氧核苷酸(CpG oligodeoxynucleotide,CpG-ODN)联合应用对小鼠移植黑素瘤的治疗效果及其可能机制。方法:制备SLC-Fc融合蛋白,体外检测SLC-Fc对小鼠淋巴细胞的趋化效应。建立小鼠黑素瘤移植模型,随机分生理盐水对照组、CpG-ODN组、SLC-Fc组以及SLC-Fc+CpG-ODN组共4组。观察治疗后各组小鼠肿瘤的生长情况,流式细胞术检测移植瘤组织中淋巴细胞的种类和浸润情况。结果:成功制备SLC-Fc蛋白,SLC-Fc对小鼠淋巴细胞具有剂量依赖性(0.03、0.3和3μg/L)趋化作用。瘤内注射SLC-Fc和(或)CpG-ODN明显抑制肿瘤的生长,联合治疗组瘤体明显小于对照组(P<0.01),并且小鼠存活时间也明显延长。联合治疗组瘤体内CD4+、CD8+T淋巴细胞和CD11c+树突状细胞较对照组显著增多(P<0.05,P<0.01),并且其肿瘤引流淋巴结也明显增大。结论:SLC和CpG-ODN联合应用对小鼠移植黑素瘤有抑制作用,其机制与趋化CD4+T、CD8+T细胞和促进DCs增殖有关。Objective：To study the therapeutic effect of secondary lymphoid tissue chemokine （SLC） combined with CpG oligodeoxynucleotide （CpG-ODN） in treatment of implanted mouse melanoma and the possible mechanism.Methods：SLC-Fc fusion protein was prepared and its chemotaxis of lymphocytes was detected by chemotaxis assay.Implanted melanoma mouse models were established and randomly divided into 4 groups：control group,SLC-Fc group,CpG-ODN group,and SLC-Fc＋CpG-ODN group.The growth of implanted tumors in each group was observed after treatment.Subtype and infiltration of lymphocytes in implanted tumor tissues were examined by flow cytometry.Results：SLC-Fc protein was successfully prepared,and it dose-dependently attracted lymphocytes （0.03,0.3,and 3 μg/L）.Intra-tumor injection SLC-Fc and CpG-ODN alone or in combination significantly inhibited growth of B16-implanted tumors.Tumor size in SLC-Fc＋CpG-ODN group was significantly smaller than that in control group （P0.01）,and animals in SLC-Fc＋CpG-ODN group survived longer.Tumor-infiltrated CD4^＋ T,CD8^＋ T,and dendritic cells （DCs） in SLC-Fc＋CpG-ODN group were markedly increased as compared with those in control group （P〈0.05）,and tumor draining lymph nodes were dramatically enlarged.Conclusion：SLC combined with CpG-ODN can inhibit the growth of implanted melanoma by attracting CD4^＋ T and CD8^＋ T and promoting proliferation of DCs.

关 键 词：次级淋巴组织趋化因子 CPG寡聚脱氧核苷酸 黑素瘤 抗肿瘤免疫 

分 类 号：R739.5[医药卫生—肿瘤] R730.54[医药卫生—临床医学]