Kontny H U, Lehrnbecher T M, Chanock S J, Mackall C L
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer Res. 1998 Dec 15;58(24):5842-9.
Fas-Fas ligand interactions play a central role in the regulation of the immune response. Fas ligand expression by tumors has been implicated in the abrogation of the host antitumor response by killing of Fas-positive effector lymphocytes. We have studied the presence and functional status of Fas and Fas ligand in Ewing's sarcoma. All Ewing's sarcoma cell lines tested expressed Fas on their surface. Three of the cell lines were readily killed after ligation of the Fas receptor. Four additional cell lines exhibited Fas-mediated apoptosis after preincubation with IFN-gamma and/or cycloheximide, whereas two cell lines were resistant to Fas-mediated killing. With regard to Fas ligand, all cell lines examined were positive for protein by immunoblot, and specificity was confirmed by reverse transcription-PCR. However, using flow cytometric analysis, Fas ligand could only be detected in Ewing's sarcoma cells after permeabilization. Furthermore, the cell lines were not capable of inducing apoptosis of Fas-sensitive Jurkat cells. In addition, Ewing's sarcoma cell lines were able to serve as stimulators for the generation of cytotoxic effector lymphocytes and were susceptible to lysis by them. Therefore, Fas ligand is expressed in Ewing's sarcoma but is not functional, suggesting that Ewing's sarcoma is a potential target for immunotherapy.
Fas-Fas配体相互作用在免疫反应调节中起核心作用。肿瘤表达Fas配体被认为可通过杀伤Fas阳性效应淋巴细胞来消除宿主抗肿瘤反应。我们研究了尤因肉瘤中Fas和Fas配体的存在及功能状态。所有检测的尤因肉瘤细胞系在其表面均表达Fas。其中三个细胞系在Fas受体被连接后很容易被杀死。另外四个细胞系在与干扰素-γ和/或环己酰亚胺预孵育后表现出Fas介导的凋亡，而两个细胞系对Fas介导的杀伤具有抗性。关于Fas配体，所有检测的细胞系通过免疫印迹法检测蛋白均呈阳性，且通过逆转录-聚合酶链反应证实了其特异性。然而，使用流式细胞术分析，只有在细胞通透后才能在尤因肉瘤细胞中检测到Fas配体。此外，这些细胞系不能诱导Fas敏感的Jurkat细胞凋亡。另外，尤因肉瘤细胞系能够作为刺激物用于产生细胞毒性效应淋巴细胞，并且易被它们裂解。因此，Fas配体在尤因肉瘤中表达但无功能，这表明尤因肉瘤是免疫治疗的潜在靶点。
