An HIF-1?/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.

ABSTRACT: 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-1?, but not HIF-2?, was essential for the effector state in CD8+ T cells. Furthermore, loss of HIF-1? 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-1?/VEGF-A axis is an essential aspect of tumor immunity.

SUBMITTER: Palazon A 

PROVIDER: S-EPMC5691891 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature