论文部分内容阅读
EB病毒(Epstein-Barrvirus,EBV)基因组编码数种恶性转化必需的蛋白质,如潜伏期膜蛋白1(latent membraneprote in1,LMP1)。LMP1能上调抗凋亡的蛋白质以支持病毒的复制,同时也能增强细胞凋亡,提示一种病毒的蛋白质既能支持病毒的生存,亦能刺激宿主的防御机制,导致受感染的细胞裂解。病灶浸润的CD8阳性T淋巴细胞通过合成Fas配体等效应分子发挥抗肿瘤免疫功能。作为一种核因子-κB(nuclearfactor-κB,NF-κB)依赖性的分子,Fas可被LMP1诱导。根据我们报道的LMP1对刺激物依赖性的细胞凋亡调节模型,LMP1能增强Fas诱导的细胞凋亡。有结果显示,Fas配体介导的细胞毒性对于EBV相关的鼻咽癌具有明显的治疗效果。近来也有报道提示,影响Fas介导细胞凋亡的基因突变可显著地降低个体对肿瘤的易感性。我们认为,在肿瘤细胞精确地调控Fas水平的细胞因子疗法,仍有可能增强癌症患者的抗肿瘤免疫。
The Epstein-Barr virus (EBV) genome encodes several proteins required for malignant transformation, such as latent membrane protein 1 (LMP1). LMP1 up-regulates anti-apoptotic proteins in support of viral replication and also enhances apoptosis, suggesting that a viral protein supports both the virus’s survival and host defense mechanisms, leading to lysis of infected cells. Foci of infiltrating CD8-positive T lymphocytes exert anti-tumor immune function through the synthesis of Fas ligand-like effector molecules. As a nuclear factor-κB (NF-κB) -dependent molecule, Fas can be induced by LMP1. According to our reported stimulus-dependent apoptosis-modulating model of LMP1, LMP1 can enhance Fas-induced apoptosis. The results show that Fas ligand-mediated cytotoxicity has a significant therapeutic effect on EBV-associated nasopharyngeal carcinoma. Recently, it has also been reported that mutations that affect Fas-mediated apoptosis may significantly reduce individual susceptibility to tumors. We believe that cytokine therapy, which precisely regulates Fas levels in tumor cells, may still enhance anti-tumor immunity in cancer patients.