肝细胞癌患者外周血淋巴细胞及肝浸润性细胞毒性淋巴细胞中Fas抗原（CD95）的表达

Expression of Fas antigen (CD95) in peripheral blood lymphocytes and in liver-infiltrating, cytotoxic lymphocytes in patients with hepatocellular carcinoma.

作者信息

Yuen M F, Hughes R D, Heneghan M A, Langley P G, Norris S

机构信息

Institute of Liver Studies, Guy's, King's, and St. Thomas' School of Medicine, London, United Kingdom.

出版信息

Cancer. 2001 Oct 15;92(8):2136-41. doi: 10.1002/1097-0142(20011015)92:8<2136::aid-cncr1555>3.0.co;2-j.

DOI:10.1002/1097-0142(20011015)92:8<2136::aid-cncr1555>3.0.co;2-j

PMID:11596030

Abstract

BACKGROUND

Fas-expressing cytotoxic T lymphocytes (CTLs) are important antitumor immune effector cells in patients with hepatocellular carcinoma (HCC). The role of transforming growth factor beta 1 (TGF-beta1) in modulating the expression of Fas by CTLs is not known in HCC. The objectives of this study were to characterize the expression of Fas by CTLs and natural killer (NK) cells among peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) in patients with HCC and to correlate the association, if any, with serum TGF-beta1 levels.

METHODS

PBLs from 18 patients with HCC and TILs from 5 HCC liver specimens were isolated, and Fas expression was analyzed by three-color flow cytometry. The results were compared with results from normal control volunteers (n = 19 individuals). Serum TGF-beta1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay.

RESULTS

The median percentage of Fas expression by CD3 positive T cells was significantly higher in patients with HCC compared with normal controls (54.37% vs. 32.03%, respectively; P = 0.0036), and this was attributable solely to Fas expression by CD4 positive PBLs (54.46% vs. 34.90%, respectively; P = 0.0234). In contrast, Fas expression was significantly higher in all the subtypes of TILs (CD3 positive, CD4 positive, CD8 positive, NK cells, and natural T cells) compared with controls (all P values were < 0.001). Tumor size was inversely proportional to the TGF-beta1 levels (correlation coefficient [r] = -0.725; P < 0.0001), which were correlated inversely with Fas expression by CD4 positive PBLs (r = -0.516; P = 0.01).

CONCLUSIONS

In patients with HCC, TILs exhibit significantly increased expression of Fas compared with PBLs that may enhance their susceptibility to apoptotic mechanisms. Larger tumors were associated with lower serum TGFbeta1 levels, and this was correlated with greater Fas expression by CD4 positive PBLs.

摘要

背景

表达Fas的细胞毒性T淋巴细胞（CTL）是肝细胞癌（HCC）患者重要的抗肿瘤免疫效应细胞。在HCC中，转化生长因子β1（TGF-β1）在调节CTL对Fas的表达方面的作用尚不清楚。本研究的目的是明确HCC患者外周血淋巴细胞（PBL）和肿瘤浸润淋巴细胞（TIL）中CTL和自然杀伤（NK）细胞Fas的表达特征，并将其与血清TGF-β1水平（若存在关联）进行相关性分析。

方法

分离18例HCC患者的PBL和5例HCC肝标本中的TIL，采用三色流式细胞术分析Fas表达。将结果与正常对照志愿者（n = 19人）的结果进行比较。采用酶联免疫吸附测定法检测HCC患者血清TGF-β1水平。

结果

与正常对照相比，HCC患者中CD3阳性T细胞Fas表达的中位数百分比显著更高（分别为54. .37%和32.03%；P = 0.0036），这完全归因于CD4阳性PBL的Fas表达（分别为54.46%和34.90%；P = 0.0234）。相反，与对照相比，所有TIL亚型（CD3阳性、CD4阳性、CD8阳性、NK细胞和自然T细胞）的Fas表达均显著更高（所有P值均<0.001）。肿瘤大小与TGF-β1水平呈负相关（相关系数[r]= -0.725；P < 0.0001），TGF-β1水平与CD4阳性PBL的Fas表达呈负相关（r = -0.516；P = 0.01）。