Department of Radiation and Cellular Oncology and The Ludwig Center for Metastasis Research, The University of Chicago, 5758 South Maryland Avenue, BOX 9006, Chicago, Illinois 60637, USA.
Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75235-9072, USA.
Nat Rev Clin Oncol. 2017 Jun;14(6):365-379. doi: 10.1038/nrclinonc.2016.211. Epub 2017 Jan 17.
Investigations into the interaction between radiotherapy and the host immune system have uncovered new mechanisms that can potentially be exploited to improve the efficacy of radiotherapy. Radiation promotes the release of danger signals and chemokines that recruit inflammatory cells into the tumour microenvironment, including antigen-presenting cells that activate cytotoxic T-cell function. By contrast, radiation can attract immunosuppressive cells into the tumour microenvironment. In rare circumstances, the antitumour effect of radiotherapy has been observed outside of the radiation field, known as the abscopal effect. This phenomenon is proposed to have an immune origin and indicates that local radiotherapy elicits systemic effects. Herein, we highlight data that provide new mechanistic explanations for the success or failure of radiotherapy, and postulate how the combination of immune-modulation and radiation could tip the balance of the host immune response to promote cure. We use the concept of radiation- induced tumour equilibrium (RITE) as a starting point to discuss the mechanistic influence of immune-checkpoint therapies on radiotherapy efficacy.
对放疗与宿主免疫系统相互作用的研究揭示了新的机制，这些机制可能被开发利用来提高放疗的疗效。放疗可促进危险信号和趋化因子的释放，将炎症细胞募集到肿瘤微环境中，包括激活细胞毒性 T 细胞功能的抗原提呈细胞。相比之下，放疗也可以吸引免疫抑制细胞进入肿瘤微环境。在极少数情况下，在放射野之外观察到放疗的抗肿瘤作用，称为远隔效应。这一现象被认为具有免疫起源，并表明局部放疗可引发全身性效应。在此，我们重点介绍了为放疗的成败提供新的机制解释的数据，并推测免疫调节与放疗的联合应用如何改变宿主免疫反应的平衡，以促进治愈。我们使用放疗诱导肿瘤平衡（RITE）的概念作为讨论免疫检查点疗法对放疗疗效的机制影响的起点。
