Revisiting the HIF switch in the tumor and its immune microenvironment.

Revisiting the HIF switch in the tumor and its immune microenvironment.
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DOI:
10.1016/j.trecan.2021.10.004
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发表时间:
2022-01
期刊:
影响因子:
18.4
通讯作者:
Koh MY
Koh MY
中科院分区:
医学1区
文献类型:
--
作者:
Cowman SJ;Koh MY

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缺氧是所有实体瘤及其转移瘤的标志。这导致缺氧诱导因子(HIF)转录因子家族的激活,其调节肿瘤微环境中肿瘤细胞和免疫细胞内的基因表达,影响肿瘤进展和治疗反应。特征最明确的 HIF 亚型 HIF-1α 和 HIF-2α 表现出不重叠且常常拮抗的作用。随着最近出现了针对一种或两种 HIF 的抑制剂,包括一流的选择性 HIF-2α 抑制剂 Belzutifan,HIF-α 异构体选择性靶向的前景现已成为现实。在这里,我们总结了在复杂的肿瘤免疫微环境背景下两种 HIF-α 亚型对肿瘤进展的独特贡献的当前知识,强调了治疗的重要考虑因素。
Hypoxia is a hallmark of all solid tumors and their metastases. This leads to activation of the hypoxia-inducible factor (HIF) family of transcription factors, which modulate gene expression within both tumor cells and immune cells within the tumor microenvironment, influencing tumor progression and treatment response. The best characterized HIF isoforms, HIF-1α and HIF-2α, show non-overlapping and often antagonistic roles. With the recent availability of inhibitors that target one or both HIFs including the first-in-class selective HIF-2α inhibitor, Belzutifan, the prospect of HIF-α isoform-selective targeting is now a reality. Here, we summarize current knowledge on the unique contributions of the two HIF-α isoforms to tumor progression in the context of the complex tumor immune microenvironment, highlighting important considerations for therapy.
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