Targeted Therapy Group, Division of Cancer Sciences, University of Manchester, UK; Cancer Research UK Lung Cancer Centre of Excellence, Manchester Cancer Research Centre, Manchester, M20 4BX, UK; The Christie NHS Foundation Trust, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M20 4BX, UK.
Targeted Therapy Group, Division of Cancer Sciences, University of Manchester, UK; Cancer Research UK Lung Cancer Centre of Excellence, Manchester Cancer Research Centre, Manchester, M20 4BX, UK.
Ann Oncol. 2018 Feb 1;29(2):301-310. doi: 10.1093/annonc/mdx790.
Despite the unheralded success of immune checkpoint blockade in delivering durable responses for some patients with non-small-cell lung cancer (NSCLC), the majority of patients do not respond. PD-L1 tumour expression and pre-existing tumour T-cell infiltration have been correlated with improved clinical outcomes to anti-PD-1/anti-PD-L1. However, patients with tumours that are negative for PD-L1 expression can also respond to treatment. Strategies to combine other treatment modalities like radiotherapy (RT) with immune checkpoint inhibitors are being investigated as means of improving the response rates to PD-1/PD-L1 antibody blockade. RT induces immunogenic changes in cancer cells, can adaptively upregulate tumour cell PD-L1 expression and can improve the efficacy of anti-PD-1/anti-PD-L1 therapy. How we design future clinical trials in NSCLC also depends on practical considerations of delivering these treatment combinations, such as RT dose, fractionation and field volume, as well as scheduling with immune checkpoint blockade. Here, we review reasons for resistance to anti-PD-1/anti-PD-L1 and how RT may be utilised in combination with these drugs to enhance their effect by building better translational research platforms.
尽管免疫检查点阻断在为一些非小细胞肺癌 (NSCLC) 患者带来持久反应方面取得了出人意料的成功，但大多数患者并没有反应。PD-L1 肿瘤表达和预先存在的肿瘤 T 细胞浸润与抗 PD-1/抗 PD-L1 的改善临床结果相关。然而，PD-L1 表达阴性的肿瘤患者也可以对治疗有反应。正在研究将其他治疗方式（如放疗 [RT]）与免疫检查点抑制剂联合使用的策略，以提高 PD-1/PD-L1 抗体阻断的反应率。RT 会在癌细胞中引起免疫原性变化，可以适应性地上调肿瘤细胞 PD-L1 表达，并提高抗 PD-1/抗 PD-L1 治疗的效果。我们在 NSCLC 中设计未来临床试验的方式也取决于这些治疗组合的实际考虑因素，例如 RT 剂量、分割和野体积，以及与免疫检查点阻断的安排。在这里，我们回顾了对抗 PD-1/抗 PD-L1 治疗的耐药性的原因，以及 RT 如何与这些药物联合使用，通过建立更好的转化研究平台来增强它们的效果。
