肝细胞性肝癌肿瘤浸润调节性T细胞的表型分析和功能探讨  

Phenotypic analysis and functional study of tumor infiltrating regulatory T cells of patients with hepatocellular carcinoma

作　　者：赵娜娜[1] 赵婷婷[2] 刑艳[2] 刘小波[2] 高小燕[2] 石统东[1] 

机构地区：[1]重庆医科大学附属第二医院感染科,400010 [2]第三军医大学全军免疫学研究所,重庆400038

出　　处：《免疫学杂志》2013年第2期115-120,共6页Immunological Journal

基　　金：国家自然科学基金课题(81172804);重庆市自然科学基金课题(CSTC 2010BB5381)

摘　　要：目的通过健康志愿者和肝细胞性肝癌(hepatocellular carcinoma,HCC)患者中调节性T细胞(Tregs)的频率和表型分析,探讨肿瘤局部浸润Treg细胞的功能和局部聚集可能的机制。方法分离健康人和HCC患者外周血单个核细胞(PBMCs)及HCC患者肝组织浸润的单个核细胞,流式检测Treg细胞频率、表型及功能特征,免疫组化检测Foxp3在肝组织内的表达。结果 CD4+Foxp3+Treg细胞在HCC患者体内明显增加且主要聚集在肿瘤局部,此外,与HCC患者自身PBMCs相比,TILs中的Treg细胞表达更高频率的功能相关分子(CTLA-4、GITR等)以及趋化因子受体CCR6和CXCR3,虽然我们发现TILs与PBMCs中Treg细胞上Ki67的表达没有统计学差异但是两者均有大约15%左右的Treg细胞为Ki67阳性。结论 HCC患者体内Treg细胞显著高于健康者及血管瘤病人;HCC患者肿瘤局部的Treg细胞比外周具有更加显著的抑制功能且局部增加的Treg细胞可能是由于局部增殖和外周趋化到局部。因此,Treg细胞的增加可能与HCC的发生及发展有密切关系。Forkhead box P3(FOXP3)+ CD4+ regulatory T(Treg) cells play a pivotal role for the maintenance of self tolerance and immune homeostasis.Recent studies have suggested that they may play a role in the regulation of liver tumor immunity.In this study,we examined the proportion of CD4+Foxp3+ T cells among CD4+T cells,which was increased in hepatocellular carcinoma(HCC) patients compared with hemangiomas patients and healthy donors.Furthermore,CD4+Foxp3+Tregs became very prominent among tumor-infiltrating Tregs during tumor response.Ex vivo analysis showed that CD4+Foxp3+ T cells were functionally active cells,suggested that they can play an important role in promoting the development and progression of HCC.In conclusion,active CD4+Foxp3+ T cells are enhanced in tumor-infiltrating lymphocytes with HCC and might potentiate CD4+Foxp3+ regulatory T cells function and contribute to the progression of HCC.

关 键 词：调节性T细胞 肝细胞性肝癌 FOXP3 

分 类 号：R735.7[医药卫生—肿瘤]