肝细胞性肝癌组织浸润淋巴细胞表型与分布研究

目的:肝细胞性肝癌组织浸润淋巴细胞与外周血T 细胞表型可能与肿瘤进展及预后相关，本研究检测肝癌患者组织及外周血T 细胞表型与分布，分析淋巴细胞表型变化与预后的关系。方法:分析2007年10月至12月中山医院147 例肝癌及癌旁组织浸润淋巴细胞表型（T 细胞或B 细胞表面标志物:CD3、CD8、CD4、CD20、CD19、Foxp 3），表型与临床病理特征及预后的关系；检测26例肝癌外周血CD3、CD8、CD4 +T细胞数量并其比例变化。结果:癌巢内肿瘤浸润细胞明显少于癌周组织（P < 0.01），癌周淋巴细胞主要分布于癌旁正常肝组织、汇管区，其与患者肝炎病史及肝硬化相关，表型以CD3 +T细胞为主，其中又以CD8 + 细胞毒性T 细胞为主；CD4 染色在多数病例为阴性，Foxp 3 仅在个别病例（15/ 109）呈阳性。肿瘤浸润淋巴细胞B 细胞标志CD20、CD19均为阴性。肿瘤组织内CD8 +T细胞浸润数量与预后正相关，而癌周浸润淋巴细胞数目与患者转移及复发无显著关系。结论:肝癌肿瘤浸润细胞在癌巢内明显少于癌周组织，肿瘤及癌周浸润细胞以CD8 + 细胞毒性T 细胞为主。肿瘤组织内CD8 +T细胞浸润数量与预后相关，而癌周浸润淋巴细胞数量与患者转移及复发无显著关系。 

Phenotype and distribution of infiltrating lymphocytes in liver cancer tissues

Objective:To identify the signature of tumor-infiltrating lymphocyte (TIL) subtypes that may affect cytokine expres -sion between different outcomes of hepatocellular carcinoma (HCC) patients by analyzing the CD molecular expression profiles of non -cancerous hepatic tissues. Methods:Surface markers of TIL in noncancerous hepatic tissues from 146 HCC patients were determined by using immunohistochemical method and flow cytometry. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier method were used to analyze the association of their expression levels with tumor recurrence and survival.Results: More than 86.4% of TILs in patients were quiescent, as measured via CD4 + or Foxp3 expression. Meanwhile, more than 90% of CD3 +T cells ex-pressed CD 8 +. The proportion of T cells was low compared with CD 8 + T cells. The proportion of CD 19and CD20in distant nontumor tissues almost was zero. The proportion of T cell subgroups isolated from HCC circulating whole blood did not show a significant shift compared with the normal control, as follows: CD4 +T/CD 8 +T =1.167 ± 1.04, CD 8 + T/CD3 +T =0.288 ± 0.116, and CD 4 +T/CD 3 +T =0.429 ± 0.178. The proportion of CD 8 + T cells in noncancerous hepatic tissues was higher than that in blood ( P<0.001). Conclusion:?TILs in HCC noncancerous hepatic tissues are increased and contain a subpopulation of CD3 +CD 8 +T cells. CD8 +T cells in cancerous tissues, rather than noncancerous tissues, show significant differences between different prognostic groups.