肝癌组织中调节性T细胞浸润与门静脉癌栓形成及其与预后的关系  

Relationship of intratumoral regulatory T cells infiltration and portal vein tumor thrombus formation with prognosis in hepatocellular carcinoma

作　　者：沈顺利[1] 陈斌[1] 付顺军[1] 匡铭[1] 梁力建[1] 彭宝岗[1] 

机构地区：[1]中山大学附属第一医院肝胆外科,广州510080

出　　处：《消化肿瘤杂志（电子版）》2013年第1期16-21,共6页Journal of Digestive Oncology(Electronic Version)

基　　金：国家自然科学基金资助项目(81071892;81272312);高等学校博士学科点专项科研基金新教师类(20100171120072)

摘　　要：目的探讨肿瘤组织中调节性T细胞(Tregs)浸润与患者临床病理特征的关系及其对患者预后的影响。方法免疫组织化学法检测76例肝癌患者肿瘤和癌旁组织中Tregs浸润情况,分析Tregs高表达、低表达与患者临床病理特征之间的关系,采用Kaplan-Meier生存分析法评估Tregs浸润对肝癌患者预后的影响。结果肿瘤组织中Tregs浸润与患者性别和门静脉癌栓显著相关(P<0.05),而与肝内多发瘤灶、HBV感染、血清AFP水平、肿瘤大小、肝硬化、肿瘤包膜完整性、Edmonson分级等无相关性(P>0.05)。Tregs低表达组DFS和TS均显著高于Tregs高表达组(P=0.012和P=0.022)。生存分析显示,肝内多发病灶、包膜有无、门静脉癌栓形成(PVTT)和瘤内Tregs浸润显著影响患者无瘤生存率(P<0.05),其他因素如年龄、性别、乙肝状态、AFP水平、Child-pugh分级、肝硬化有无、Edmonson分级、癌旁和瘤内CD4+、CD8+T细胞浸润等均对患者DFS无显著影响(P>0.05)。上述因素中,仅PVTT和瘤内Tregs浸润显著影响患者总体生存率(P<0.05)。多因素风险模型分析,包膜完整与否(OR=1.816,95%CI:1.084-3.041,P=0.023)和瘤内Tregs浸润(OR=1.931,95%CI:1.153-3.233,P=0.012)是影响患者DFS的独立预后因素;瘤内Tregs浸润(OR=1.843,95%CI:1.073-3.166,P=0.027)是影响患者OS的独立预后因素。结论肿瘤组织中Tregs高表达的肝癌患者预后不良,Tregs高表达有可能促进PVTT形成,Tregs有可能成为肝癌免疫治疗的作用靶点。Objective To investigate the relationship of intratumoral regulatory T cells(Tregs)infiltration with clinicopathological features and prognosis of hepatocellular carcinoma(HCC) patients.Methods Immunohistochemical method was used to examine CD4+,CD8+T cells and Foxp3 + Tregs infiltration in tissues adjacent to cancer and tumor tissues from 76 HCC patients. The relationship of intratumoral regulatory T cells(Tregs) infiltration with clinicopathological features and prognosis of hepatocellular carcinoma(HCC) patients was analysized. Results Intratumoral Tregs infiltration was correlated with sex and portal vein tumor thrombus formation(P<0.05), but not with multiple lesions,HBV infection, serum AFP level, tumor size, hepatocirrhosis, complete capsule or not, and Edmonson classifications. The disease-free survival(DFS) and overall survival(OS) were significantly higher in high Tregs expression group than those in low Tregs expression group. Survival analysis revealed that DFS was significantly associated with multiple lesions, complete capsule or not, PVTT and intratumoral Tregs infiltration, but not with age, sex, HBV infection, AFP level, hepatocirrhosis, Child and Edmonson classifications, while OS were only significantly associated with PVTT and intratumoral Tregs infiltration.Cox proportional hazard model analysis revealed that complete capsule or not(OR =1.816,95% CI:1.084-3.041,P=0.023)and intratumoral Tregs infiltration(OR=1.931,95%CI:1.153-3.233,P=0.012)were independent prognostic factors for DFS, while only Tregs infiltration(OR=1.843, 95%CI: 1.073-3.166,P=0.027) for OS. Conclusions Intratumoral Tregs infiltration is associated with PVTT and a poorer prognosis. It is hopeful that Tregs will be used as a new therapeutic target.

关 键 词：肝细胞癌 调节性T细胞 门静脉癌栓 免疫治疗 

分 类 号：R735.7[医药卫生—肿瘤]