{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:27:41Z","timestamp":1784132861625,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772779"],"award-info":[{"award-number":["81772779"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273199"],"award-info":[{"award-number":["82273199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20221417"],"award-info":[{"award-number":["BK20221417"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To investigate the role of mammalian target of rapamycin (mTOR) signal in Toll\u2010like receptor (TLR) 8\u2010mediated regulation of glucose metabolism and its effect on reversing immunosuppression in CD4<jats:sup>+<\/jats:sup> regulatory T\u2010cells (Tregs) in ovarian cancer (OC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fluorescence\u2010activated cell sorting was used to detect the expression levels of mTOR<jats:sup>+<\/jats:sup> and 4E\u2010BP1<jats:sup>+<\/jats:sup> cells in CD4<jats:sup>+<\/jats:sup> Tregs. The prognosis and immune infiltration analysis of mTOR mRNA in OC were performed using the TIMER and Kaplan\u2013Meier plotter database. Furthermore, real\u2010time polymerase chain reaction (RT\u2010PCR) and western blot (WB) were used to detect expression levels of glucose metabolism\u2010related genes and proteins in CD4<jats:sup>+<\/jats:sup> Tregs. Glucose uptake and glycolysis levels were detected by colorimetry, while the effects of CD4<jats:sup>+<\/jats:sup> Tregs on the proliferation of CD4<jats:sup>+<\/jats:sup> T\u2010effector cells (Teffs) were evaluated by carboxyfluorescein diacetate succinimidyl ester (CFSE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>mTOR expression in CD4<jats:sup>+<\/jats:sup> Tregs was significantly higher in patients with OC compared with controls and in CD4<jats:sup>+<\/jats:sup> Tregs than in CD4<jats:sup>+<\/jats:sup> Teffs in OC. Additionally, the expression level of mTOR mRNA was related to prognosis and immune infiltration levels in patients with OC. Blocking the mTOR signal resulted in downregulation of glucose metabolism in CD4<jats:sup>+<\/jats:sup> Tregs. Simultaneous inhibition of the mTOR signal while activation of the TLR8 signal had a coordinated inhibitory effect on glucose metabolism and the immunosuppressive function of CD4<jats:sup>+<\/jats:sup> Tregs. Furthermore, the mTOR signal played an essential role in TLR8\u2010mediated reversal of immunosuppressive function in CD4<jats:sup>+<\/jats:sup> Tregs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings imply that activation of the TLR8 signal inhibits glucose metabolism in CD4<jats:sup>+<\/jats:sup> Tregs by downregulating mTOR signaling, thereby reversing the immunosuppressive function of these cells in an OC cell growth environment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6247","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T05:43:37Z","timestamp":1686807817000},"page":"16310-16322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Glucose metabolism and function of <scp>CD4<\/scp><sup>+<\/sup> Tregs are regulated by the <scp>TLR8<\/scp>\/<scp>mTOR<\/scp> signal in an environment of <scp>SKOV3<\/scp> cell growth"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6729-6788","authenticated-orcid":false,"given":"Ming","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine the First Affiliated Hospital of Nanjing Medical University  Nanjing China"},{"name":"Branch of National Clinical Research Center for Laboratory Medicine  Nanjing China"},{"name":"Department of Clinical Laboratory Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine the First Affiliated Hospital of Nanjing Medical University  Nanjing China"},{"name":"Branch of National Clinical Research Center for Laboratory Medicine  Nanjing 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