Immunology Section, Department of Medicine, University of Verona, 37134, Verona, Italy.
Ovarian Cancer Research Center (OCRC), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Semin Immunol. 2018 Feb;35:35-47. doi: 10.1016/j.smim.2018.02.002. Epub 2018 Feb 26.
Angiogenesis is a hallmark of cancer and a requisite that tumors must achieve to fulfill their metabolic needs of nutrients and oxygen. As a critical step in cancer progression, the 'angiogenic switch' allows tumor cells to survive and grow, and provides them access to vasculature resulting in metastatic progression and dissemination. Tumor-dependent triggering of the angiogenic switch has critical consequences on tumor progression which extends from an increased nutrient supply and relies instead on the ability of the tumor to hijack the host immune response for the generation of a local immunoprivileged microenvironment. Tumor angiogenic-mediated establishment of endothelial anergy is responsible for this process. However, tumor endothelium can also promote immune tolerance by unbalanced expression of co-stimulatory and co-inhibitory molecules and by releasing soluble factors that restrain T cell function and induce apoptosis. In this review, we discuss the molecular properties of the tumor endothelial barrier and endothelial anergy and discuss the main immunosuppressive mechanisms triggered by the tumor endothelium. Lastly, we describe the current anti-angiogenic therapeutic landscape and how targeting tumor angiogenesis can contribute to improve clinical benefits for patients.
血管生成是癌症的一个标志，也是肿瘤必须实现的必要条件，以满足其营养物质和氧气的代谢需求。作为癌症进展的关键步骤，“血管生成开关”允许肿瘤细胞存活和生长，并为它们提供血管，导致转移进展和扩散。肿瘤依赖性触发血管生成开关对肿瘤进展有重要影响，从增加营养供应扩展到依赖肿瘤劫持宿主免疫反应以产生局部免疫特惠微环境的能力。肿瘤血管生成介导的内皮失能负责这一过程。然而，肿瘤内皮细胞也可以通过不平衡表达共刺激和共抑制分子以及通过释放抑制 T 细胞功能和诱导细胞凋亡的可溶性因子来促进免疫耐受。在这篇综述中，我们讨论了肿瘤内皮屏障和内皮失能的分子特性，并讨论了肿瘤内皮触发的主要免疫抑制机制。最后，我们描述了当前的抗血管生成治疗领域以及靶向肿瘤血管生成如何有助于改善患者的临床获益。
