An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.
An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.
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DOI：
10.1016/j.ccell.2017.10.003
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发表时间：
2017-11-13
期刊：
影响因子：
50.3
通讯作者：
Johnson RS
中科院分区：
文献类型：
--
作者：
Palazon A;Tyrakis PA;Macias D;Veliça P;Rundqvist H;Fitzpatrick S;Vojnovic N;Phan AT;Loman N;Hedenfalk I;Hatschek T;Lövrot J;Foukakis T;Goldrath AW;Bergh J;Johnson RS
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. HIF-1α drives CD8+ T cell migration and effector function HIF-1α loss in T cells accelerates tumor growth Loss of VEGF-A in T cells accelerates tumor growth Loss of VEGF-A in T cells results in increased chemotherapeutic response 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.
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影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
10.1
作者：
Hodi FS;Lawrence D;Lezcano C;Wu X;Zhou J;Sasada T;Zeng W;Giobbie-Hurder A;Atkins MB;Ibrahim N;Friedlander P;Flaherty KT;Murphy GF;Rodig S;Velazquez EF;Mihm MC Jr;Russell S;DiPiro PJ;Yap JT;Ramaiya N;Van den Abbeele AD;Gargano M;McDermott D
通讯作者：
McDermott D
影响因子：
64.8
作者：
Gerber, HP;Malik, AK;Ferrara, N
通讯作者：
Ferrara, N
影响因子：
64.5
作者：
Dang EV;Barbi J;Yang HY;Jinasena D;Yu H;Zheng Y;Bordman Z;Fu J;Kim Y;Yen HR;Luo W;Zeller K;Shimoda L;Topalian SL;Semenza GL;Dang CV;Pardoll DM;Pan F
通讯作者：
Pan F
影响因子：
5.4
作者：
Goel, Shom;Wong, Andus Hon-Kit;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.