國家衛生研究院 NHRI:Item 3990099045/10481
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10481


    Title: Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor-bearing hosts through prevention of ROS-mediated apoptosis
    Authors: Jian, SL;Chen, WW;Su, YC;Su, YW;Chuang, TH;Hsu, SC;Huang, LR
    Contributors: Institute of Molecular and Genomic Medicine;Division of Vaccine Research and Development;Immunology Research Center
    Abstract: Immunotherapy aiming to rescue or boost antitumor immunity is an emerging strategy for treatment of cancers. The efficacy of immunotherapy is strongly controlled by the immunological milieu of cancer patients. Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cell populations with immunosuppressive functions accumulating in individuals during tumor progression. The signaling mechanisms of MDSC activation have been well studied. However, there is little known about the metabolic status of MDSCs and the physiological role of their metabolic reprogramming. In this study, we discovered that myeloid cells upregulated their glycolytic genes when encountered with tumor-derived factors. MDSCs exhibited higher glycolytic rate than their normal cell compartment did, which contributed to the accumulation of the MDSCs in tumor-bearing hosts. Upregulation of glycolysis prevented excess reactive oxygen species (ROS) production by MDSCs, which protected MDSCs from apoptosis. Most importantly, we identified the glycolytic metabolite, phosphoenolpyruvate (PEP), as a vital antioxidant agent able to prevent excess ROS production and therefore contributed to the survival of MDSCs. These findings suggest that glycolytic metabolites have important roles in the modulation of fitness of MDSCs and could be potential targets for anti-MDSC strategy. Targeting MDSCs with analogs of specific glycolytic metabolites, for example, 2-phosphoglycerate or PEP may diminish the accumulation of MDSCs and reverse the immunosuppressive milieu in tumor-bearing individuals.
    Date: 2017-05-11
    Relation: Cell Death and Disease. 2017 May 11;8(5):Article number e2779.
    Link to: http://dx.doi.org/10.1038/cddis.2017.192
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-4889&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000402195700045
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85019224300
    Appears in Collections:[Li-Rung Huang] Periodical Articles
    [Shu-Ching Hsu] Periodical Articles
    [Tsung-Hsien Chuang] Periodical Articles
    [Yu-Wen Su] Periodical Articles

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