Control of the immune response by pro-angiogenic factors.
Control of the immune response by pro-angiogenic factors.
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DOI：
10.3389/fonc.2014.00070
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发表时间：
2014
影响因子：
4.7
通讯作者：
Terme M
中科院分区：
文献类型：
--
作者：
Voron T;Marcheteau E;Pernot S;Colussi O;Tartour E;Taieb J;Terme M
正常细胞逐渐转化为癌细胞的特点是获得八个标志。在这些标准中，癌细胞避免免疫破坏的能力已被注意到。因此，肿瘤发展成为免疫系统不可见的机制，例如免疫抑制细胞的诱导，这能够抑制有效免疫反应的发展。肿瘤微环境中产生的分子参与了免疫抑制微环境的发生。最近，研究表明血管内皮生长因子A （VEGF-A）除了具有促血管生成活性外，还具有免疫抑制特性。VEGF-A可诱导未成熟树突状细胞、髓源性抑制细胞、调节性T细胞聚集，抑制T淋巴细胞向肿瘤的迁移。其他促血管生成因子如胎盘生长因子（PlGF）也可能参与肿瘤诱导的免疫抑制，但这方面的研究很少。在这里，我们回顾了促血管生成因子（特别是VEGF-A）对免疫细胞的影响。靶向VEGF-A/VEGFR轴的抗血管生成分子在过去几十年中已经被开发出来，通常用于治疗癌症患者。这些药物具有抗血管生成的特性，但也可以抵消肿瘤诱导的免疫抑制。基于这些免疫调节特性，抗血管生成分子可以在临床前模型中有效地与免疫治疗策略相关联。这些组合目前正在癌症患者中进行研究。
The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction has been noted. Thus, tumors develop mechanisms to become invisible to the immune system, such as the induction of immunosuppressive cells, which are able to inhibit the development of an efficient immune response. Molecules produced in the tumor microenvironment are involved in the occurrence of an immunosuppressive microenvironment. Recently, it has been shown that vascular endothelial growth factor A (VEGF-A) exhibits immunosuppressive properties in addition to its pro-angiogenic activities. VEGF-A can induce the accumulation of immature dendritic cells, myeloid-derived suppressor cells, regulatory T cells, and inhibit the migration of T lymphocytes to the tumor. Other pro-angiogenic factors such as placental growth factor (PlGF) could also participate in tumor-induced immunosuppression, but only few works have been performed on this point. Here, we review the impact of pro-angiogenic factors (especially VEGF-A) on immune cells. Anti-angiogenic molecules, which target VEGF-A/VEGFR axis, have been developed in the last decades and are commonly used to treat cancer patients. These drugs have anti-angiogenic properties but can also counteract the tumor-induced immunosuppression. Based on these immunomodulatory properties, anti-angiogenic molecules could be efficiently associated with immunotherapeutic strategies in preclinical models. These combinations are currently under investigation in cancer patients.