Hypoxia-inducible factors enhance the effector responses of CD8 + T cells to persistent antigen
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...Additionally, rewiring the metabolic activity of TILs, as demonstrated herein and elsewhere (Doedens et al., 2013), could pose a new strategy for enhancing the potency and durability of ACT....
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...…CD8 T cells with increased PD-1 expression fail to fully activatemTORor aerobic glycolysis following TCR stimulation and conversely, those with hyper-HIF1a activity and aerobic glycolysis are refractory to functional exhaustion (Doedens et al., 2013; Parry et al., 2005; Staron et al., 2014)....
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...Deletion of its negative regulator, von Hippel-Lindau (VHL), enhances HIF-1–mediated CD8 T cell glycolysis and effector responses to persistent viral infection (Doedens et al., 2013)....
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...The up-regulation of transcription factors c-Myc, estrogenrelated receptor (ERR), and hypoxia inducible factor-1 (HIF-1) coordinately drives the expression of genes involved in intermediary metabolism that fuel the rapid proliferation of effector T cells during clonal expansion (Michalek et al., 2011b; Wang et al., 2011; Doedens et al., 2013)....
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...Deletion of its negative regulator, von Hippel-Lindau (VHL), enhances HIF-1–mediated CD8 T cell glycolysis and effector responses to persistent viral infection (Doedens et al., 2013)....
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...…estrogenrelated receptor (ERR), and hypoxia inducible factor-1 (HIF-1) coordinately drives the expression of genes involved in intermediary metabolism that fuel the rapid proliferation of effector T cells during clonal expansion (Michalek et al., 2011b; Wang et al., 2011; Doedens et al., 2013)....
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