Cardi G, Heaney J A, Schned A R, Ernstoff M S
Division of Medical Oncology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA.
Cancer Res. 1998 May 15;58(10):2078-80.
The functional expression of Fas-ligand on tumor cells reported in a variety of neoplasms has been proposed by several groups as a mechanism of tumor escape from immunological detection. To better support this hypothesis, we have evaluated and quantified for the first time the presence of the Fas(CD95)-R molecule on tumor-infiltrating lymphocytes and on matched peripheral blood lymphocytes (PBLs) of renal cell cancer patients. By two-color flow cytometry we have detected a significant increase in the Fas(CD95)-R expression on tumor-infiltrating lymphocytes compared with matched patient and normal volunteer PBLs. We also observed a decreased expression of the Fas(CD95)-R expression on PBLs from renal cell cancer patients compared with normal healthy controls. The Fas(CD95)-R expression was observed predominantly on the CD4+ subset in all three groups. These different distributions of the Fas(CD95)-R molecule support the hypothesis that the Fas(CD95)-R/Fas(CD95)-L pathway and tumor microenvironment play a major role in the modulation of T-cell function and differentiation to either memory and activation or apoptosis.
多个研究小组提出,多种肿瘤中肿瘤细胞上Fas配体的功能性表达是肿瘤逃避免疫检测的一种机制。为了更好地支持这一假说,我们首次评估并定量检测了肾细胞癌患者肿瘤浸润淋巴细胞及配对外周血淋巴细胞(PBL)上Fas(CD95)受体分子的存在情况。通过双色流式细胞术,我们检测到与配对患者及正常志愿者的PBL相比,肿瘤浸润淋巴细胞上Fas(CD95)受体的表达显著增加。我们还观察到,与正常健康对照相比,肾细胞癌患者PBL上Fas(CD95)受体的表达降低。在所有三组中,Fas(CD95)受体的表达主要见于CD4+亚群。Fas(CD95)受体分子的这些不同分布支持了以下假说:Fas(CD95)受体/Fas(CD95)配体途径及肿瘤微环境在调节T细胞功能以及向记忆和活化或凋亡方向分化中起主要作用。