The mechanisms by which regulatory T cells (Tregs) migrate to and function within the hypoxic tumor microenvironment are unclear. Our studies indicate that specific ablation of hypoxia-inducible factor 1α (HIF-1α) in Tregs results in enhanced CD8+ T cell suppression versus wild-type Tregs under hypoxia, due to increased pyruvate import into the mitochondria. Importantly, HIF-1α-deficient Tregs are minimally affected by the inhibition of lipid oxidation, a fuel that is critical for Treg metabolism in tumors. Under hypoxia, HIF-1α directs glucose away from mitochondria, leaving Tregs dependent on fatty acids for mitochondrial metabolism within the hypoxic tumor. Indeed, inhibition of lipid oxidation enhances the survival of mice with glioma. Interestingly, HIF-1α-deficient-Treg mice exhibit significantly enhanced animal survival in a murine model of glioma, due to their stymied migratory capacity, explaining their reduced abundance in tumor-bearing mice. Thus HIF-1α acts as a metabolic switch for Tregs between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression.
Pubmed ID: 30943404 RIS Download
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A free reference manager and academic social network to organize your research, collaborate with others online, and discover the latest research. Automatically generate bibliographies, Collaborate easily with other researchers online, Easily import papers from other research software, Find relevant papers based on what you're reading, Access your papers from anywhere online, Read papers on the go with the iPhone app. The software, Mendeley Desktop, offers: * Automatic extraction of document details * Efficient management of your papers * Sharing and synchronization of your library (or parts of it) * Additional features: A plug-in for citing your articles in Microsoft Word, OCR (image-to-text conversion, so you can full-text search all your scanned PDFs), etc The website, Mendeley Web, complements Mendeley Desktop by offering these features: * An online back up of your library * Statistics of all things interesting * A research network that allows you to keep track of your colleagues' publications, conference participations, awards etc * A recommendation engine for papers that might interest you
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