Cytotoxic T cells infiltrating tumors are thought to utilize HIF transcription factors during adaptation to the hypoxic tumor microenvironment. Deletion analyses of the two key HIF isoforms found that HIF-1α, but not HIF-2α, was essential for the effector state in CD8⁺ T cells. Furthermore, loss of HIF-1α in CD8⁺ T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. Deletion of VEGF-A, an HIF target gene, in CD8⁺ T cells accelerated tumorigenesis while also altering vascularization. Analyses of human breast cancer showed inverse correlations between VEGF-A expression and CD8⁺ T cell infiltration, and a link between T cell infiltration and vascularization. These data demonstrate that the HIF-1α/VEGF-A axis is an essential aspect of tumor immunity.

中文翻译：

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细胞毒性 T 细胞中的 HIF-1α/VEGF-A 轴调节肿瘤进展。

浸润肿瘤的细胞毒性 T 细胞被认为在适应缺氧肿瘤微环境的过程中利用 HIF 转录因子。对两个关键 HIF 亚型的删除分析发现，HIF-1α（而非 HIF-2α）对于 CD8 ⁺ T 细胞的效应状态至关重要。^{此外，CD8 +} T细胞中HIF-1α的缺失减少了肿瘤浸润和肿瘤细胞杀伤，并改变了肿瘤血管化。^{CD8 +} T 细胞中 VEGF-A（一种 HIF 靶基因）的缺失会加速肿瘤发生，同时也会改变血管形成。对人类乳腺癌的分析表明，VEGF-A 表达与 CD8 ⁺ T 细胞浸润之间呈负相关，并且 T 细胞浸润与血管化之间存在联系。这些数据表明 HIF-1α/VEGF-A 轴是肿瘤免疫的重要方面。