Fig. 3: PGE₂ rewires metabolism of TILs.

a, Heat map of normalized expression, z-scored by row, of the top differentially expressed Hallmark signatures (P < 0.05) between unstimulated and RA CD8⁺ T cells treated with PGE₂ for 24 h or untreated. P values (left column) indicate significance of differences between control and PGE₂-treated RA CD8⁺ T cells in three patients (n = 3). P values (false discovery rate, Bonferroni-corrected) were calculated by applying GSEA on the average expression per group. b,c, Violin plot representation of fold changes in reaction rates of the inferred metabolic states for RA CD8⁺ T cells (b; n = 3) and CD8⁺ TILs (c; n = 1) upon 24 h exposure to PGE₂. ETC, electron transport chain; PIP, phosphoinositide. d, Heat map representation of polar metabolites in CD8⁺ TILs upon PGE₂ treatment (n = 4). P values (left column) were calculated using two-tailed paired t-test for the peak areas of the corresponding metabolites. e, ATP quantification by ELISA in CD8⁺ TILs treated for 24 h with PGE₂, EP2/EP4 antagonists or combined treatment (n = 5). Data are mean ± s.d. One-way ANOVA with Dunnett’s post hoc test for multiple comparisons (e). Independent biological samples were used; exact numbers of biological replicates are listed in each panel.