Chappell D B, Restifo N P
The Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda MD 20814, USA.
Cancer Immunol Immunother. 1998 Oct;47(2):65-71. doi: 10.1007/s002620050505.
Fas (Apo-1/CD95) is a cell-surface protein that is responsible for initiating a cascade of proteases (caspases) culminating in apoptotic cell death in a variety of cell types. The function of the Fas/FasL system in the dampening of immune responses to infectious agents through the autocrine deletion of activated T cells has been well documented. More recently, it has been proposed that tumor cells express FasL, presumably to avoid immune detection. In this review, we focus on the role of the interaction of Fas and FasL in the modulation of antitumor responses. We critically examine the evidence that FasL is expressed by tumor cells and explore alternative explanations for the observed phenomena in vitro and in vivo. By reviewing data that we have generated in our laboratory as well as reports from the literature, we will argue that the Fas/FasL system is a generalized mechanism used in an autocrine fashion to regulate cell survival and expansion in response to environmental and cellular cues. We propose that FasL expression by tumor cells, when present, is indicative of a perturbed balance in the control of proliferation while "immune privilege" is established by "suicide" of activated antitumor T cells, a form of activation-induced cell death.
Fas（Apo-1/CD95）是一种细胞表面蛋白，负责启动一系列蛋白酶（半胱天冬酶），最终导致多种细胞类型发生凋亡性细胞死亡。Fas/FasL系统通过自分泌方式清除活化的T细胞，从而抑制对感染因子的免疫反应，这一功能已得到充分证实。最近，有人提出肿瘤细胞表达FasL，可能是为了逃避免疫检测。在这篇综述中，我们重点关注Fas与FasL相互作用在调节抗肿瘤反应中的作用。我们严格审查了肿瘤细胞表达FasL的证据，并探讨了体外和体内观察到的现象的其他解释。通过回顾我们实验室产生的数据以及文献报道，我们认为Fas/FasL系统是一种以自分泌方式调节细胞存活和增殖的普遍机制，以应对环境和细胞信号。我们提出，肿瘤细胞表达FasL（如果存在）表明在增殖控制中平衡受到干扰，而“免疫豁免”是通过活化的抗肿瘤T细胞“自杀”建立的，这是一种活化诱导的细胞死亡形式。
