Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Molecular Pharmacology Group, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
Nat Rev Clin Oncol. 2021 Aug;18(8):527-540. doi: 10.1038/s41571-021-00496-y. Epub 2021 Apr 8.
Immune checkpoint inhibitors have revolutionized medical oncology, although currently only a subset of patients has a response to such treatment. A compelling body of evidence indicates that anti-angiogenic therapy has the capacity to ameliorate antitumour immunity owing to the inhibition of various immunosuppressive features of angiogenesis. Hence, combinations of anti-angiogenic agents and immunotherapy are currently being tested in >90 clinical trials and 5 such combinations have been approved by the FDA in the past few years. In this Perspective, we describe how the angiogenesis-induced endothelial immune cell barrier hampers antitumour immunity and the role of endothelial cell anergy as the vascular counterpart of immune checkpoints. We review the antitumour immunity-promoting effects of anti-angiogenic agents and provide an update on the current clinical successes achieved when these agents are combined with immune checkpoint inhibitors. Finally, we propose that anti-angiogenic agents are immunotherapies - and vice versa - and discuss future research priorities.
免疫检查点抑制剂已经彻底改变了肿瘤医学，尽管目前只有一部分患者对这种治疗有反应。大量证据表明，抗血管生成疗法具有改善抗肿瘤免疫的能力，因为它抑制了血管生成的各种免疫抑制特征。因此，目前正在 90 多项临床试验中测试抗血管生成药物与免疫疗法的联合应用，并且在过去几年中，有 5 种此类联合疗法已获得 FDA 批准。在本观点中，我们描述了血管生成诱导的内皮免疫细胞屏障如何阻碍抗肿瘤免疫，以及内皮细胞失能作为免疫检查点的血管对应物的作用。我们回顾了抗血管生成药物对抗肿瘤免疫的促进作用，并提供了这些药物与免疫检查点抑制剂联合应用时目前取得的临床成功的最新信息。最后，我们提出抗血管生成药物既是免疫疗法，反之亦然，并讨论了未来的研究重点。
