School of Medical Sciences, Griffith Health Institute, Griffith University, Parklands Ave., Gold Coast, Queensland 4222, Australia.
Curr Pharm Biotechnol. 2013;14(3):357-76. doi: 10.2174/1389201011314030010.
Cytotoxic drugs in cancer therapy are used with the expectation of selectively killing and thereby eliminating the offending cancer cells. If they should die in an appropriate manner, the cells can also release danger signals that promote an immune reaction that reinforces the response against the cancer. The identity of these immune-enhancing danger signals, how they work extra- and intracellularly, and the molecular mechanisms by which some anti-cancer drugs induce cell death to bring about the release of danger signals are the major focus of this review. A specific group of mitocans, the vitamin E analogs that act by targeting mitochondria to drive ROS production and also promote a more immunogenic means of cancer cell death exemplify such anti-cancer drugs. The role of reactive oxygen species (ROS) production and the events leading to the activation of the inflammasome and pro-inflammatory mediators induced by dying cancer cell mitochondria are discussed along with the evidence for their contribution to promoting immune responses against cancer. Current knowledge of how the danger signals interact with immune cells to boost the anti-tumor response is also evaluated.
细胞毒性药物在癌症治疗中被用于选择性地杀死肿瘤细胞。如果这些细胞以适当的方式死亡，它们还可以释放危险信号，促进免疫反应，从而增强对癌症的反应。这些免疫增强危险信号的身份、它们在细胞内外的作用方式以及一些抗癌药物诱导细胞死亡以释放危险信号的分子机制是本综述的主要重点。一组特定的 mitocans，即通过靶向线粒体来驱动 ROS 产生并促进更具免疫原性的癌细胞死亡方式的维生素 E 类似物，就是这样的抗癌药物的例子。本文讨论了活性氧 (ROS) 产生的作用以及导致凋亡小体激活和促炎介质诱导的事件，以及它们对促进抗肿瘤免疫反应的贡献的证据。还评估了当前关于危险信号如何与免疫细胞相互作用以增强抗肿瘤反应的知识。
