Glucose metabolism and function of CD4 + Tregs are regulated by the TLR8 / mTOR signal in an environment of SKOV3 cell growth

作者：Ming Wu, Xin Fu, Rui Xu, Shuna Liu, Rong Li, Juan Xu, Wenwen Shang, Xian Chen, Ting Wang, Fang Wang · 发表于：Cancer Medicine · 年份：2023 · DOI：10.1002/cam4.6247 · 被引用次数：8 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

Abstract Purpose To investigate the role of mammalian target of rapamycin (mTOR) signal in Toll‐like receptor (TLR) 8‐mediated regulation of glucose metabolism and its effect on reversing immunosuppression in CD4 + regulatory T‐cells (Tregs) in ovarian cancer (OC). Methods Fluorescence‐activated cell sorting was used to detect the expression levels of mTOR + and 4E‐BP1 + cells in CD4 + Tregs. The prognosis and immune infiltration analysis of mTOR mRNA in OC were performed using the TIMER and Kaplan–Meier plotter database. Furthermore, real‐time polymerase chain reaction (RT‐PCR) and western blot (WB) were used to detect expression levels of glucose metabolism‐related genes and proteins in CD4 + Tregs. Glucose uptake and glycolysis levels were detected by colorimetry, while the effects of CD4 + Tregs on the proliferation of CD4 + T‐effector cells (Teffs) were evaluated by carboxyfluorescein diacetate succinimidyl ester (CFSE). Results mTOR expression in CD4 + Tregs was significantly higher in patients with OC compared with controls and in CD4 + Tregs than in CD4 + 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 + 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 + Tregs. Furt...