Kebin Liu, Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912, United States.
World J Gastrointest Oncol. 2010 Nov 15;2(11):399-406. doi: 10.4251/wjgo.v2.i11.399.
The host immune system functions as a guardian against tumor development. It has been demonstrated that cytotoxic T lymphocyte (CTL)-mediated cytotoxic pathways function to inhibit or delay human colorectal cancer development. However, the host anti-tumor immune responses also 'edit' the tumor and select for more aggressive variants, resulting in immune evasion and tumor escape. Fas is a death receptor that mediates one of the major cytotoxic effector mechanisms of the CTLs. Fas is highly expressed in normal human colon epithelial cells but is frequently silenced in colorectal carcinoma, especially in metastatic colorectal carcinoma, suggesting that loss of Fas expression and function may be an immune evasion and tumor escape mechanism. In addition, recent studies indicated that Fas also mediates cellular proliferation signaling pathways to promote tumor development. Therefore, the death receptor Fas may not only transduce death signals to suppress tumor development but also activate cellular proliferation and the migration process to promote tumor growth and progression. Thus, understanding the mechanisms by which the Fas receptor and its associated protein complex transduces the death and survival signals may identify molecular targets for the development of therapeutic strategy to enhance the Fas-mediated death signals to increase the efficacy of cancer immunotherapy.
宿主免疫系统作为对抗肿瘤发生的守护者。已证实细胞毒性 T 淋巴细胞（CTL）介导的细胞毒性途径可抑制或延迟人结直肠癌的发展。然而，宿主抗肿瘤免疫反应也“编辑”肿瘤并选择更具侵袭性的变体，导致免疫逃逸和肿瘤逃逸。Fas 是一种死亡受体，介导 CTL 的主要细胞毒性效应机制之一。Fas 在正常的人结肠上皮细胞中高度表达，但在结直肠癌中经常失活，特别是在转移性结直肠癌中，表明 Fas 表达和功能的丧失可能是一种免疫逃逸和肿瘤逃逸机制。此外，最近的研究表明，Fas 还介导细胞增殖信号通路以促进肿瘤的发展。因此，死亡受体 Fas 不仅可以传递死亡信号来抑制肿瘤的发展，还可以激活细胞增殖和迁移过程，促进肿瘤的生长和进展。因此，了解 Fas 受体及其相关蛋白复合物传递死亡和存活信号的机制可能为开发治疗策略以增强 Fas 介导的死亡信号，从而提高癌症免疫治疗的疗效提供分子靶标。
