Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes
Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes
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DOI：
10.1038/s41571-021-00496-y
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发表时间：
2021-04-08
影响因子：
78.8
通讯作者：
Griffioen, Arjan W.
中科院分区：
文献类型：
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作者：
Huinen, Zowi R.;Huijbers, Elisabeth J. M.;Griffioen, Arjan W.
抗血管生成治疗具有改善抗肿瘤免疫的能力，因此，抗血管生成药物和免疫治疗的一些组合已被批准，其中一些正在测试中。作者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，以及内皮细胞无反应性作为免疫检查点的血管对应物的作用。免疫检查点抑制剂已经彻底改变了医学肿瘤学，尽管目前只有一部分患者对这种治疗有反应。一个令人信服的证据表明，抗血管生成治疗有能力改善抗肿瘤免疫，由于抑制血管生成的各种免疫抑制功能。因此，抗血管生成剂和免疫疗法的组合目前正在90多个临床试验中进行测试，并且在过去几年中，FDA已经批准了5种这样的组合。在这个角度来看，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和内皮细胞无反应性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的抗肿瘤免疫促进作用，并提供了这些药物与免疫检查点抑制剂联合使用时所取得的最新临床成功。最后，我们提出，抗血管生成剂是免疫疗法-反之亦然-并讨论未来的研究重点。
Anti-angiogenic therapy has the capacity to ameliorate antitumour immunity and, thus, some combinations of anti-angiogenics and immunotherapies have been approved and a number of them are being tested. The authors of this Perspective describe how the angiogenesis-induced endothelial immune cell barrier hampers antitumour immunity and the role of endothelial cell anergy as a vascular counterpart of immune checkpoints.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.