Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
Vaccine. 2010 Jun 23;28(29):4566-72. doi: 10.1016/j.vaccine.2010.04.074. Epub 2010 May 6.
Premature death of the adoptively transferred cytolytic T lymphocytes (CTL) by means of activation induced cell death (AICD) represents one of the major constraints in devising an effective anti-cancer immune intervention strategy. Understanding the mechanism of AICD is, therefore, critical for developing methods to interfere with this death process. Although the existing paradigm on AICD centers around the initiation of the cascade of events originating from the engagement of death receptors leading to the activation of effector caspases and eventually resulting in cell death, recent findings have questioned the universal role of caspases as the cell death executioners. We here review our current understanding of the contribution of caspase-dependent and caspase-independent death executioners in AICD of T cells. We will also discuss the involvement of mitochondria-centric death pathway in AICD of human tumor associated antigen-specific primary CTL and its implications in cancer immunotherapy.
通过激活诱导的细胞死亡 (AICD) 导致细胞毒性 T 淋巴细胞 (CTL) 的过早死亡是设计有效抗癌免疫干预策略的主要限制因素之一。因此，了解 AICD 的机制对于开发干扰此死亡过程的方法至关重要。尽管关于 AICD 的现有范例主要集中在起始于死亡受体结合引发的级联反应，从而激活效应半胱天冬酶，最终导致细胞死亡的事件上，但最近的发现质疑了半胱天冬酶作为细胞死亡执行者的普遍作用。我们在这里回顾了我们对 caspase 依赖性和 caspase 非依赖性死亡执行者在 T 细胞 AICD 中的作用的现有认识。我们还将讨论线粒体中心死亡途径在人类肿瘤相关抗原特异性原代 CTL 的 AICD 中的作用及其在癌症免疫治疗中的意义。
