Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer.
Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer.
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DOI：
10.3390/cancers12113145
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发表时间：
2020-10-27
期刊：
影响因子：
5.2
通讯作者：
Pentheroudakis G
中科院分区：
文献类型：
--
作者：
Ntellas P;Mavroeidis L;Gkoura S;Gazouli I;Amylidi AL;Papadaki A;Zarkavelis G;Mauri D;Karpathiou G;Kolettas E;Batistatou A;Pentheroudakis G
尽管VEGF-A被认为是癌症血管生成的主要参与者，但有关其与肿瘤微环境其他成分相互作用的新数据也出现了。在这里，我们回顾了VEGF-A对癌细胞和免疫细胞的作用，以及研究和建立的抗血管生成药物与免疫检查点抑制剂的联合治疗。因此，我们详细阐述了这些新型组合方法发展背后的科学原理。血管生成一直被认为可以促进和维持癌症的生长，这使得破坏血管内皮生长因子/受体（VEGF/VEGFR）通路的抗血管生成药物的引入成为21世纪初的一个重要里程碑。最初对VEGF信号的研究主要集中在其对内皮细胞的生存和有丝分裂作用，迄今为止抗血管生成治疗取得了中等成功。然而，VEGF可以通过直接影响和促进肿瘤细胞的存活、增殖和侵袭以及促进免疫抑制微环境，对包括免疫细胞和肿瘤细胞在内的其他细胞类型产生多种影响。在这篇综述中，我们总结了VEGF/VEGFR通路对非内皮细胞的影响，以及由此产生的抗血管生成药物的意义，包括直接抑制肿瘤细胞生长和免疫刺激功能。最后，我们介绍了先前未被重视的VEGF生物学研究，这些研究通过破坏VEGF/VEGFR通路证明了免疫调节特性和肿瘤消退，现在为免疫治疗与抗血管生成药物的新联合治疗提供了科学基础。
Although VEGF-A is well characterized as the principal player of cancer angiogenesis, new data on the interplay with other components of the tumor microenvironment emerge. Here we review the effect of VEGF-A on cancer cells and immune cells as well as investigative and established combinational therapies of anti-angiogenic agents with immune checkpoint inhibitors. We thus elaborate the scientific rationale behind the development of these novel combinational approaches. Angiogenesis has long been considered to facilitate and sustain cancer growth, making the introduction of anti-angiogenic agents that disrupt the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway an important milestone at the beginning of the 21st century. Originally research on VEGF signaling focused on its survival and mitogenic effects towards endothelial cells, with moderate so far success of anti-angiogenic therapy. However, VEGF can have multiple effects on additional cell types including immune and tumor cells, by directly influencing and promoting tumor cell survival, proliferation and invasion and contributing to an immunosuppressive microenvironment. In this review, we summarize the effects of the VEGF/VEGFR pathway on non-endothelial cells and the resulting implications of anti-angiogenic agents that include direct inhibition of tumor cell growth and immunostimulatory functions. Finally, we present how previously unappreciated studies on VEGF biology, that have demonstrated immunomodulatory properties and tumor regression by disrupting the VEGF/VEGFR pathway, now provide the scientific basis for new combinational treatments of immunotherapy with anti-angiogenic agents.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
17.1
作者：
Allen E;Jabouille A;Rivera LB;Lodewijckx I;Missiaen R;Steri V;Feyen K;Tawney J;Hanahan D;Michael IP;Bergers G
通讯作者：
Bergers G
影响因子：
4.4
作者：
Bouzin, Caroline;Brouet, Agnes;Feron, Olivier
通讯作者：
Feron, Olivier
影响因子：
5
作者：
Attar-Schneider, Oshrat;Drucker, Liat;Lishner, Michael
通讯作者：
Lishner, Michael
影响因子：
8.8
作者：
Alfaro, C.;Suarez, N.;Gonzalez, A.;Solano, S.;Erro, L.;Dubrot, J.;Palazon, A.;Hervas-Stubbs, S.;Gurpide, A.;Lopez-Picazo, J. M.;Grande-Pulido, E.;Melero, I.;Perez-Gracia, J. L.
通讯作者：
Perez-Gracia, J. L.