Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.
Nat Rev Clin Oncol. 2019 Dec;16(12):729-745. doi: 10.1038/s41571-019-0238-9. Epub 2019 Jun 26.
Immunotherapy, specifically the introduction of immune checkpoint inhibitors, has transformed the treatment of cancer, enabling long-term tumour control even in individuals with advanced-stage disease. Unfortunately, only a small subset of patients show a response to currently available immunotherapies. Despite a growing consensus that combining immune checkpoint inhibitors with radiotherapy can increase response rates, this approach might be limited by the development of persistent radiation-induced immunosuppression. The ultimate goal of combining immunotherapy with radiotherapy is to induce a shift from an ineffective, pre-existing immune response to a long-lasting, therapy-induced immune response at all sites of disease. To achieve this goal and enable the adaptation and monitoring of individualized treatment approaches, assessment of the dynamic changes in the immune system at the patient level is essential. In this Review, we summarize the available clinical data, including forthcoming methods to assess the immune response to radiotherapy at the patient level, ranging from serum biomarkers to imaging techniques that enable investigation of immune cell dynamics in patients. Furthermore, we discuss modelling approaches that have been developed to predict the interaction of immunotherapy with radiotherapy, and highlight how they could be combined with biomarkers of antitumour immunity to optimize radiotherapy regimens and maximize their synergy with immunotherapy.
免疫疗法，特别是免疫检查点抑制剂的引入，改变了癌症的治疗方式，使即使是晚期疾病的患者也能实现长期肿瘤控制。不幸的是，目前可用的免疫疗法只有一小部分患者有反应。尽管越来越多的人认为将免疫检查点抑制剂与放射治疗相结合可以提高反应率，但这种方法可能会受到持续的放射诱导免疫抑制的限制。将免疫疗法与放射治疗相结合的最终目标是诱导从无效的、预先存在的免疫反应转变为在疾病的所有部位都能持久的、治疗诱导的免疫反应。为了实现这一目标并能够适应和监测个体化治疗方法，在患者水平上评估免疫系统的动态变化至关重要。在这篇综述中，我们总结了现有的临床数据，包括即将出现的用于评估患者水平放射治疗免疫反应的方法，从血清生物标志物到成像技术，这些方法可以研究患者免疫细胞的动态变化。此外，我们讨论了已经开发出的用于预测免疫疗法与放射治疗相互作用的建模方法，并强调了如何将其与抗肿瘤免疫的生物标志物相结合，以优化放射治疗方案并最大限度地发挥其与免疫疗法的协同作用。
