The convergence of radiation and immunogenic cell death signaling pathways.
The convergence of radiation and immunogenic cell death signaling pathways.
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DOI：
10.3389/fonc.2012.00088
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发表时间：
2012
影响因子：
4.7
通讯作者：
Formenti SC
中科院分区：
文献类型：
--
作者：
Golden EB;Pellicciotta I;Demaria S;Barcellos-Hoff MH;Formenti SC
电离辐射（IR）通过多种高度调控的过程触发肿瘤细胞的程序性细胞死亡。辐射诱导的肿瘤细胞死亡已经在体外进行了广泛的研究，并被广泛地归因于多种不同的机制，包括细胞凋亡、坏死、有丝分裂突变（MC）、自噬和衰老，这些可能同时发生。当考虑肿瘤细胞在生物体中的死亡时，越来越多的证据表明存在一种相互关系，即辐射刺激免疫系统，而免疫系统反过来又有助于肿瘤细胞的死亡。因此，在体外对辐射诱导的肿瘤细胞死亡的传统测量不能代表临床观察到的反应程度，包括局部区域失败率的降低以及无转移和总生存期的改善。因此，了解辐射诱导的细胞死亡类型的免疫反应是至关重要的。本文综述了辐射诱导肿瘤细胞死亡的机制，重点介绍了免疫原性细胞死亡（ICD）。将放疗与特异性化疗或免疫疗法相结合的策略能够诱导一系列癌症特异性免疫原，不仅可以通过增强细胞杀伤，还可以通过诱导成功的抗肿瘤疫苗来提高患者的生存率，从而增强肿瘤控制。
Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill. As a result, traditional measurements of radiation-induced tumor cell death, in vitro, fail to represent the extent of clinically observed responses, including reductions in loco-regional failure rates and improvements in metastases free and overall survival. Hence, understanding the immunological responses to the type of radiation-induced cell death is critical. In this review, the mechanisms of radiation-induced tumor cell death are described, with particular focus on immunogenic cell death (ICD). Strategies combining radiotherapy with specific chemotherapies or immunotherapies capable of inducing a repertoire of cancer specific immunogens might potentiate tumor control not only by enhancing cell kill but also through the induction of a successful anti-tumor vaccination that improves patient survival.