肾细胞癌患者肿瘤浸润淋巴细胞与外周淋巴细胞中Fas及Fas配体的差异表达

Different expression of Fas and Fas ligand in tumor infiltrating and peripheral lymphocytes of patients with renal cell carcinomas.

作者信息

Elsässer-Beile Ursula, Gierschner Dorothee, Welchner Tanja, Wetterauer Ulrich

机构信息

Department of Urology, University of Freiburg, Stefan-Meier Str. 8, D-79106 Freiburg, Germany.

出版信息

Anticancer Res. 2003 Jan-Feb;23(1A):433-7.

PMID:12680244

Abstract

BACKGROUND

The presence of tumor infiltrating lymphocytes (TIL) in renal cell carcinomas (RCC) is thought to reflect a host-mediated immune response against the tumor and the Fas/Fas ligand--based lytic pathway is a major mechanism of T lymphocyte--mediated cytotoxicity. The aim of the present study was to investigate the expression of Fas and Fas ligand (FasL) in freshly-isolated pure TIL as compared to autologous peripheral blood lymphocytes (PBL), in order to determine their activation status.

MATERIALS AND METHODS

The mRNA expression of Fas and FasL was compared in freshly-isolated CD3(+)-, CD4(+)- and CD8(+)-TIL and matched autologous CD3(+)-, CD4(+)- and CD8(+)-PBL. The TIL were isolated from mechanically disaggregated tumor material and PBL from peripheral blood by gradient centrifugation and subsequent selection with magnetic beads. In these pure lymphocyte preparations the constitutive expression of Fas and FasL was determined by using a semiquantitative PCR-assisted mRNA amplification assay.

RESULTS

In the CD3(+)-TIL of 20 patients with RCC (group 1), mRNA levels of FasL were significantly higher than in the matched autologous CD3(+)-PBL (p < or = 0.01) whereas Fas expression was not different in both populations. In a second group of 20 patients (group 2), we found a significantly higher expression of FasL in the CD8(+)-TIL compared to the CD8(+)-PBL (p < or = 0.001) and also in the CD4(+)-TIL compared to the CD4(+)-PBL (p < or = 0.001).

CONCLUSION

The higher expression of FasL in the TIL compared to autologous PBL reflects an in vivo activation and lytic potency of the lymphocytes in the tumor surrounding.

摘要

背景

肾细胞癌（RCC）中肿瘤浸润淋巴细胞（TIL）的存在被认为反映了宿主针对肿瘤的免疫反应，而基于Fas/Fas配体的溶解途径是T淋巴细胞介导的细胞毒性的主要机制。本研究的目的是调查新鲜分离的纯TIL中Fas和Fas配体（FasL）与自体外周血淋巴细胞（PBL）相比的表达情况，以确定它们的激活状态。

材料与方法

比较新鲜分离的CD3(+)、CD4(+)和CD8(+) - TIL以及匹配的自体CD3(+)、CD4(+)和CD8(+) - PBL中Fas和FasL的mRNA表达。TIL从机械解离的肿瘤组织中分离，PBL从外周血中通过梯度离心及随后用磁珠分选获得。在这些纯淋巴细胞制剂中，通过半定量PCR辅助的mRNA扩增测定法确定Fas和FasL的组成性表达。

结果

在20例RCC患者（第1组）的CD3(+) - TIL中，FasL的mRNA水平显著高于匹配的自体CD3(+) - PBL（p≤0.01），而Fas在两个群体中的表达无差异。在另一组20例患者（第2组）中，我们发现CD8(+) - TIL中FasL的表达显著高于CD8(+) - PBL（p≤0.001），CD4(+) - TIL中FasL的表达也显著高于CD4(+) - PBL（p≤0.001）。