Biological Sciences Platform, Sunnybrook Research Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Nat Rev Clin Oncol. 2018 May;15(5):310-324. doi: 10.1038/nrclinonc.2018.9. Epub 2018 Feb 13.
Immunotherapies have revolutionized medical oncology following the remarkable and, in some cases, unprecedented outcomes observed in certain groups of patients with cancer. Combination with other therapeutic modalities, including anti-angiogenic agents, is one of the many strategies currently under investigation to improve the response rates and duration of immunotherapies. Such a strategy might seem counterintuitive given that anti-angiogenic agents can increase tumour hypoxia and reduce the number of blood vessels within tumours. Herein, we review the additional effects mediated by drugs targeting VEGF-dependent signalling and other pathways, such as those mediated by angiopoietin 2 or HGF, which might increase the efficacy of immunotherapies. In addition, we discuss the seldom considered possibility that immunotherapies, and immune-checkpoint inhibitors in particular, might increase the efficacy of anti-angiogenic or other types of antivascular therapies and/or promote changes in the tumour vasculature. In short, we propose that interactions between both therapeutic modalities could be considered a 'two-way street'.
免疫疗法在癌症治疗领域掀起了一场革命,在某些癌症患者群体中观察到了显著的、在某些情况下是前所未有的疗效。与其他治疗方式(包括抗血管生成药物)联合使用是目前正在研究的众多策略之一,旨在提高免疫疗法的反应率和持续时间。考虑到抗血管生成药物会增加肿瘤缺氧并减少肿瘤内的血管数量,这种策略似乎有违直觉。在此,我们综述了靶向 VEGF 依赖性信号通路和其他通路的药物(如血管生成素 2 或 HGF 介导的通路)所介导的附加效应,这些效应可能会提高免疫疗法的疗效。此外,我们还讨论了免疫疗法(特别是免疫检查点抑制剂)可能会提高抗血管生成或其他类型的抗血管治疗的疗效,以及促进肿瘤血管变化的这一鲜少被考虑到的可能性。简而言之,我们提出,这两种治疗方式之间的相互作用可以被视为“双向车道”。