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- W4313381446 abstract "Abstract Regulatory T (Treg) cells induce an immunosuppressive microenvironment that is a major obstacle to successful tumor immunotherapy. Dissecting the regulations between energy metabolism and functionality in human Treg cells will provide insights for developing novel immunotherapies against cancer. We discovered that human naturally occurring Treg (nTreg) and tumor-associated Treg cells exhibit distinct metabolic profiles with predominant dependence on glucose metabolism compared with effector T cells. Activated nTreg and tumor-associated Treg cells depend on accelerated glucose consumption for their cellular senescence induction and suppressive activity in responder T cells during their cross-talk. We further identified that TLR8 signaling selectively inhibits glucose uptake and suppresses metabolic processes of glycolysis in human Treg cells, resulting in reversal of Treg suppressive function and cellular senescence induction. In addition, TLR8 signaling activation downregulates mTORC1-HIF1α signaling in Treg cells that control molecular processes of Treg glucose metabolism and suppressive functions. Our in vivo studies further demonstrated that TLR8 signaling-mediated reprogramming of glucose metabolism and function in human Treg cells can enhance anti-tumor immunity and immunotherapy efficacy in a melanoma adoptive transfer T cell therapy model. These studies identify novel mechanistic links between innate signaling and metabolic regulation of human Treg suppression, and provide a new strategy and concept for tumor immunotherapy." @default.
- W4313381446 created "2023-01-06" @default.
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- W4313381446 date "2019-05-01" @default.
- W4313381446 modified "2023-09-27" @default.
- W4313381446 title "Reprograming human Treg metabolism via innate TLR signaling for tumor immunotherapy" @default.
- W4313381446 doi "https://doi.org/10.4049/jimmunol.202.supp.137.9" @default.
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