Hypoxia is a universal feature of solid cancers caused by a mismatch between cellular oxygen supply and consumption. To meet the increased demand for oxygen, hypoxic cancer cells (CCs) induce a multifaceted process known as angiogenesis, wherein new vessels are formed by the sprouting of pre-existing ones. In addition to providing oxygen for growth and an exit route for dissemination, angiogenic vessels and factors are co-opted by CCs to enable the generation of an immunotolerant, hypoxic tumor microenvironment, leading to therapeutic failure and mortality. In this review, we discuss how hypoxia-inducible factors (HIFs), the mechanistic target of rapamycin (mTOR), and the unfolded protein response (UPR) control angiogenic factors serving both vascular and immunomodulatory functions in the tumor microenvironment. Possible therapeutic strategies, wherein targeting oxygen sensing might enhance anti-angiogenic and immunologically-mediated anti-cancer responses, are suggested.

低氧是由细胞供氧和供氧不匹配引起的实体癌的普遍特征。为了满足对氧气的不断增长的需求，低氧癌细胞（CCs）诱导了一个被称为血管生成的多方面过程，其中新血管是通过现有血管的萌芽形成的。除了为生长提供氧气和传播途径外，CC还选择了血管生成血管和因子，以产生免疫耐受的低氧肿瘤微环境，从而导致治疗失败和死亡。在这篇综述中，我们讨论了缺氧诱导因子（HIF），雷帕霉素（mTOR）的机制靶标和未折叠的蛋白应答（UPR）如何控制在肿瘤微环境中同时具有血管和免疫调节功能的血管生成因子。可能的治疗策略，