Voron Thibault, Marcheteau Elie, Pernot Simon, Colussi Orianne, Tartour Eric, Taieb Julien, Terme Magali
INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France.
INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France ; Service d'Hépatogastroentérologie et d'Oncologie Digestive, Hôpital Européen Georges Pompidou , Paris , France.
Front Oncol. 2014 Apr 2;4:70. doi: 10.3389/fonc.2014.00070. eCollection 2014.
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.
正常细胞向癌细胞的渐进性转变具有八个特征。在这些标准中，癌细胞逃避免疫破坏的能力已被注意到。因此，肿瘤发展出对免疫系统不可见的机制，例如诱导免疫抑制细胞，这些细胞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形成。最近的研究表明，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细胞的积累，并抑制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，但关于这一点的研究较少。在这里，我们综述促血管生成因子（特别是VEGF-A）对免疫细胞的影响。在过去几十年中，已经开发出靶向VEGF-A/VEGFR轴的抗血管生成分子，并且通常用于治疗癌症患者。这些药物具有抗血管生成特性，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，抗血管生成分子在临床前模型中可以有效地与免疫治疗策略联合使用。目前正在癌症患者中对这些联合治疗进行研究。
