Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.
Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, People's Republic of China.
Mol Cancer. 2022 Sep 8;21(1):177. doi: 10.1186/s12943-022-01645-2.
Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.
鉴于缺氧是许多不同实体瘤的持续生理特征，也是癌症恶性的关键驱动因素，因此它最近被认为是癌症治疗的主要靶点。肿瘤相关巨噬细胞（TAMs）是肿瘤微环境（TME）中最丰富的免疫细胞，它们对肿瘤的发展和免疫治疗有很大的影响。TAMs 在缺氧的肿瘤区域大量积聚。TAMs 和缺氧代表了一个致命的组合，因为缺氧被认为会诱导促肿瘤发生的巨噬细胞表型。缺氧不仅直接影响巨噬细胞极化，还通过改变肿瘤细胞和巨噬细胞之间的通讯产生间接影响。例如，缺氧会影响趋化因子和外泌体的表达，这两者都会对受体细胞产生深远的影响。最近，已经证明癌细胞和 TAMs 在缺氧 TME 中的复杂相互作用与不良预后和增加肿瘤恶性程度有关。然而，目前还没有关于肿瘤细胞和 TAMs 之间缺氧介导的通讯的综合文献综述。因此，本综述旨在收集关于这一主题的所有最新数据，并为开发减少缺氧影响的新型治疗策略提供见解。
