An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression
(2017) In Cancer Cell 32(5). p.5-683- 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. 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... (More)
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. Palazon et al. demonstrate the importance of the HIF-1α/VEGF-A axis in tumor immunity. HIF-1α, but not HIF-2α, drives CD8+ T cell glycolytic metabolism, migration, and effector function, while the HIF-1α transcriptional target VEGF-A contributes to tumor vascularization.
(Less)
- author
- organization
- publishing date
- 2017-11-13
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- angiogenesis, cytotoxic T cells, HIF transcription factors, hypoxia, immunotherapy, VEGF
- in
- Cancer Cell
- volume
- 32
- issue
- 5
- pages
- 5 - 683
- publisher
- Cell Press
- external identifiers
-
- pmid:29136509
- wos:000414965900015
- scopus:85033695630
- ISSN
- 1535-6108
- DOI
- 10.1016/j.ccell.2017.10.003
- language
- English
- LU publication?
- yes
- id
- 874575c6-2836-43d1-8cdc-ddb17bda2a7b
- date added to LUP
- 2017-11-28 07:17:09
- date last changed
- 2024-10-29 18:46:11
@article{874575c6-2836-43d1-8cdc-ddb17bda2a7b, abstract = {{<p>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<sup>+</sup> T cells. Furthermore, loss of HIF-1α in CD8<sup>+</sup> T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. Deletion of VEGF-A, an HIF target gene, in CD8<sup>+</sup> T cells accelerated tumorigenesis while also altering vascularization. Analyses of human breast cancer showed inverse correlations between VEGF-A expression and CD8<sup>+</sup> 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. Palazon et al. demonstrate the importance of the HIF-1α/VEGF-A axis in tumor immunity. HIF-1α, but not HIF-2α, drives CD8<sup>+</sup> T cell glycolytic metabolism, migration, and effector function, while the HIF-1α transcriptional target VEGF-A contributes to tumor vascularization.</p>}}, author = {{Palazon, Asis and Tyrakis, Petros A. and Macias, David and Veliça, Pedro and Rundqvist, Helene and Fitzpatrick, Susan and Vojnovic, Nikola and Phan, Anthony T. and Loman, Niklas and Hedenfalk, Ingrid and Hatschek, Thomas and Lövrot, John and Foukakis, Theodoros and Goldrath, Ananda W. and Bergh, Jonas and Johnson, Randall S.}}, issn = {{1535-6108}}, keywords = {{angiogenesis; cytotoxic T cells; HIF transcription factors; hypoxia; immunotherapy; VEGF}}, language = {{eng}}, month = {{11}}, number = {{5}}, pages = {{5--683}}, publisher = {{Cell Press}}, series = {{Cancer Cell}}, title = {{An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression}}, url = {{http://dx.doi.org/10.1016/j.ccell.2017.10.003}}, doi = {{10.1016/j.ccell.2017.10.003}}, volume = {{32}}, year = {{2017}}, }