Fig. 7: Effects of PGE2-EP4 signaling on mitochondrial respiration and glycolysis in CD8+ T cells.

a, b Extracellular flux analysis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in TCR-activated naïve CD8+ T cells in the presence or absence of PGE2 and the indicated antagonists. Naïve CD8+ T cells were activated using anti-CD3/CD28 Dynabeads in the presence of 30 IU/ml r-IL2 either with or without 30 nM PGE2 and/or the indicated antagonist for 60 h. Data are mean ± SD, n = 5. b One-way ANOVA with Sidak’s multiple comparison test. *P < 0.05. **P < 0.01, ***P < 0.001, ****P < 0.0001. Representative results from two independent experiments are shown. c Heatmaps showing time-dependent downregulation of glycolysis-related genes in TCR-activated CD8+ T cells incubated with PGE2. n = 3 per condition. d GSEA plot of DEGs between PTGER4hi and PTGER4lo CD8+ T cells (top) and TIM cells from human tumor (bottom) for MOOTHA glycolysis gene set. P-values were estimated using adaptive multilevel splitting Monte Carlo approach and adjusted by Benjamini–Hochberg procedure. e Dot plot illustrating the downregulation of genes in REACTOME_GLYCOLYSIS pathway in PTGER4hi CD8+ T cells, CD4+ T cells, and TIM. Statistical analysis was performed using the two-sided Wilcoxon Rank Sum Test. Source data and exact P-values are provided as a Source Data file.