Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa

• Published in: Nature reviews. Clinical oncology Vol. 15; no. 5; pp. 310 - 324
• Main Authors: Khan, Kabir A., Kerbel, Robert S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2018; Nature Publishing Group
• Subjects: 631/154/51/1568; 631/67/327; 692/4028/67/1059/2325; 692/4028/67/2328; 692/4028/67/322; Angiogenesis; Angiogenesis inhibitors; Angiopoietin; Blood vessels; Cancer; Cancer research; Cancer treatment; Carcinogenesis; Dosage and administration; Drug delivery; Health aspects; Hypoxia; Immune checkpoint inhibitors; Immunosuppressive agents; Immunotherapy; Medicine & Public Health; Methods; Oncology; Physiological aspects; review-article; Signal transduction; Tumors; Vascular endothelial growth factor
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/nrclinonc.2018.9

Key Points Proteins with major roles in angiogenesis can also have direct or indirect effects on components of the immune system, most often resulting in immunosuppressive outcomes The tumour vasculature can upregulate or downregulate proteins that control the homing and trafficking of immune cells, creating a selective immune-cell barrier on endothelium The use of anti-angiogenic drugs and other vascular-targeting agents can normalize and remodel the tortuous tumour vasculature, enabling alleviation of hypoxia and efficient tumour infiltration by effector immune cells Combinations of anti-angiogenic agents with various immunotherapies, including immune-checkpoint inhibitors, have been shown preclinically to generate more-potent antitumour effects and might have clinical potential Anti-angiogenic agents can alleviate immunosuppression, and conversely, immunotherapies can induce changes in the vasculature or bring about antivascular effects; thus, immunotherapy and/or anti-angiogenic therapies have the potential to create a cycle of immunostimulation and vascular remodelling within tumours The combination of immunotherapies with other therapeutic modalities, including anti-angiogenic agents, is currently under investigation to improve the outcomes of patients receiving immunotherapies. In this article, the authors review the effects mediated by anti-angiogenic agents that might increase the efficacy of immunotherapies and discuss the possibility that immunotherapies might increase the efficacy of anti-angiogenic agents and/or promote changes in the tumour vasculature. 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'.