Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Services, Royal Marsden NHS Foundation Trust, London, UK.
Lancet. 2021 Mar 13;397(10278):1010-1022. doi: 10.1016/S0140-6736(20)32598-8. Epub 2020 Dec 4.
Several tumour types are responsive to immunotherapy, as shown by regulatory approvals for immune checkpoint inhibitors. However, many patients either do not respond or do not have durable clinical benefit. Thus, there is great interest in developing predictors of response to immunotherapy and rational combination therapies that can enhance efficacy by overcoming primary and acquired resistance. In this Review, we provide an assessment of immunotherapy response biomarkers that can identify patients who will benefit from monotherapy rather than from combinations. We review the rationale for combination therapy and different strategies, including combinations with chemotherapy, targeted therapy, radiation therapy, intratumoural therapies, other immunomodulators, and adaptive cell therapy, including chimeric antigen T-cell receptors and other novel T-cell receptor-based therapies. There are many combination partners in development; therefore, a programmatic approach is needed to develop a framework for biomarker-driven combination therapy selection.
几种肿瘤类型对免疫疗法有反应，这从免疫检查点抑制剂的监管批准中可以看出。然而，许多患者要么没有反应，要么没有持久的临床获益。因此，人们非常关注开发免疫疗法反应的预测因子和合理的联合疗法，通过克服原发性和获得性耐药来提高疗效。在这篇综述中，我们评估了免疫疗法反应的生物标志物，可以识别出将从单药治疗而不是联合治疗中获益的患者。我们回顾了联合治疗的基本原理和不同策略，包括与化疗、靶向治疗、放射治疗、肿瘤内治疗、其他免疫调节剂以及适应性细胞治疗（包括嵌合抗原 T 细胞受体和其他新型基于 T 细胞受体的疗法）的联合。有许多联合治疗药物正在开发中；因此，需要采用程序化方法来制定基于生物标志物的联合治疗选择框架。
