Shurin G V, Gerein V, Lotze M T, Barksdale E M
University of Pittsburgh Cancer Institute, Division of Pediatric Surgery, Children's Hospital of Pittsburgh, PA 15213, USA.
Nat Immun. 1998;16(5-6):263-74. doi: 10.1159/000069452.
The CD95/CD95L (Fas/Fas ligand) receptor/ligand system plays an important role in regulation of cell survival and induction of a programmed cell death. It is also involved in regulation of effector phase of T and NK cell cytotoxicity, establishment of immune privilege sites, and tumor escape from immune recognition. In this study, we assessed expression of CD95L in tumors obtained from patients with neuroblastoma (NB) and in established NB cell lines. We measured the presence of intratumoral T cell infiltrates and T cell survival in tumor tissue samples. High levels of apoptosis were observed in tumor-associated lymphocytes as well as in Jurkat T cells cocultured with NB cells in vitro. T cell death was reduced after treatment of NB cells (in vitro) with antibody to FAS ligand (FasL). Overall, our data suggest that NB-induced apoptosis of Fas-sensitive Jurkat T cells is mediated by functional FasL expressed on NB and Fas/FasL interaction may be responsible for the elimination of T cells in the NB microenvironment.
CD95/CD95L(Fas/Fas配体)受体/配体系统在细胞存活调控及程序性细胞死亡诱导过程中发挥着重要作用。它还参与T细胞和NK细胞细胞毒性效应阶段的调控、免疫豁免部位的建立以及肿瘤逃避免疫识别。在本研究中,我们评估了神经母细胞瘤(NB)患者肿瘤组织及已建立的NB细胞系中CD95L的表达情况。我们检测了肿瘤组织样本中瘤内T细胞浸润情况及T细胞存活情况。在肿瘤相关淋巴细胞以及体外与NB细胞共培养的Jurkat T细胞中均观察到高水平的凋亡现象。用抗FAS配体(FasL)抗体处理NB细胞(体外)后,T细胞死亡减少。总体而言,我们的数据表明,NB诱导的Fas敏感型Jurkat T细胞凋亡是由NB上表达的功能性FasL介导的,Fas/FasL相互作用可能是NB微环境中T细胞消除的原因。