肝细胞性肝癌组织浸润淋巴细胞表型与分布研究

Phenotype and distribution of infiltrating lymphocytes in liver cancer tissues

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、Foxp3),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,Foxp3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。

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 CDS＋. The proportion of T cells was low compared with CDS＋ T cells. The proportion of CD 19 and CD20 in 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/CDS＋T = 1.167 ± 1.04, CDS＋ T/CD3＋T = 0.288 ± 0.116, and CD4＋T/CD3＋T = 0.429 ± 0.178. The proportion of CDS＋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＋CD8＋T cells. CDS＋T cells in cancerous tissues, rather than noncancerous tissues, show significant differences between different prognostic groups.