Institut Gustave Roussy, Villejuif, France.
Cancer J. 2011 Sep-Oct;17(5):351-8. doi: 10.1097/PPO.0b013e3182325d4d.
For a long time, anticancer therapies were believed to work (and hence convey a therapeutic benefit) either by killing cancer cells or by inducing a permanent arrest in their cell cycle (senescence). In both scenarios, the efficacy of anticancer regimens was thought to depend on cancer cell-intrinsic features only. More recently, the importance of the tumor microenvironment (including stromal and immune cells) has been recognized, along with the development of therapies that function by modulating tumor cell-extrinsic pathways. In particular, it has been shown that some chemotherapeutic and radiotherapeutic regimens trigger cancer cell death while stimulating an active immune response against the tumor. Such an immunogenic cell death relies on the coordinated emission of specific signals from dying cancer cells and their perception by the host immune system. The resulting tumor-specific immune response is critical for the eradication of tumor cells that may survive therapy. In this review, we discuss the molecular mechanisms that underlie the vaccine-like effects of some chemotherapeutic and radiotherapeutic regimens, with particular attention to the signaling pathways and genetic elements that constitute the prerequisites for immunogenic anticancer therapy.
长期以来，人们认为抗癌疗法（因此具有治疗益处）要么通过杀死癌细胞，要么通过诱导其细胞周期永久停滞（衰老）来发挥作用。在这两种情况下，抗癌方案的疗效都被认为仅取决于癌细胞内在特征。最近，人们已经认识到肿瘤微环境（包括基质和免疫细胞）的重要性，同时也开发了通过调节肿瘤细胞外在途径起作用的疗法。特别是，已经表明一些化疗和放疗方案在刺激针对肿瘤的主动免疫应答的同时触发癌细胞死亡。这种免疫原性细胞死亡依赖于垂死癌细胞从协调释放特定信号及其被宿主免疫系统感知。由此产生的肿瘤特异性免疫应答对于消除可能在治疗后存活的肿瘤细胞至关重要。在这篇综述中，我们讨论了一些化疗和放疗方案产生类似疫苗效果的分子机制，特别关注构成免疫原性抗癌治疗先决条件的信号通路和遗传元件。
