An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.
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Authors
Tyrakis, Petros A
Fitzpatrick, Susan
Vojnovic, Nikola
Phan, Anthony T
Loman, Niklas
Hatschek, Thomas
Goldrath, Ananda W
Bergh, Jonas
Publication Date
2017-11Journal Title
Cancer cell
ISSN
1535-6108
Publisher
Elsevier
Volume
32
Issue
5
Pages
669-683.e5
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print
Metadata
Show full item recordCitation
Palazon, A., Tyrakis, P. A., Macias, D., Veliça, P., Rundqvist, H., Fitzpatrick, S., Vojnovic, N., et al. (2017). An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.. Cancer cell, 32 (5), 669-683.e5. https://doi.org/10.1016/j.ccell.2017.10.003
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-1α, but not HIF-2α, was essential for the effector state in CD8+ T cells. Further, loss of HIF-1α in CD8+ T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. Deletion of VEGF-A, a 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.
Keywords
CD8-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Cells, Cultured, Cell Line, Tumor, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Breast Neoplasms, Neoplasms, Experimental, Disease Progression, Neovascularization, Pathologic, Vascular Endothelial Growth Factor A, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Female, Hypoxia-Inducible Factor 1, alpha Subunit
Sponsorship
Wellcome Trust (092738/Z/10/Z)
European Commission (331756)
National Cancer Institute (NCI) (R01CA153983)
Wellcome Trust (214283/Z/18/Z)
Identifiers
External DOI: https://doi.org/10.1016/j.ccell.2017.10.003
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276369
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