Fig. 1: The PGE₂–EP2/EP4 axis is associated with decreased IL-2-mediated TIL expansion.

a, Representation of the translational research pipeline of a phase I melanoma TIL-ACT trial. Figure created with BioRender.com. b, Correlation between IL-2 signalling score from pseudobulked patient CD8⁺ TILs and total numbers of TILs at pre-REP (on day 11) from patients with melanoma enrolled in the TIL-ACT trial (n = 13). c, Representation of Reactome pathways that are anti-correlated with IL-2 signalling score from pseudobulked patient CD8⁺ TILs (no correction for multiple testing applied) (n = 13). PCC, Pearson’s correlation score. d, Correlation between IL-2 signalling score and eicosanoid ligand-binding receptor score from pseudobulked patient CD8⁺ TILs (n = 13). e, Violin plot of PGE₂ signature score in tumour-reactive versus non-tumour-reactive CD8⁺ TILs subsets that expanded or did not expand in the cell therapy product. The number of cells is shown at the top of the graph. Box plots display smallest and largest values in the dataset, box hinges represent first and third quartiles with the centre as median and whiskers extend to 1.5× the interquartile range from the first and third quartiles. EM-like, effector memory-like; Pex, precursor exhausted; Tex, terminal exhausted; ISG, IFN-stimulated gene. f, Correlation per patient between baseline PGE₂ levels in the supernatant of expanding TILs from tumour fragments and total numbers of pre-REP TILs in a phase I solid tumour TIL-ACT trial (n = 18). g, Correlation per patient between PGE₂ levels in the supernatant of expanding TILs from tumour fragments of breast (n = 20) and melanoma (n = 12) and total numbers of pre-REP TILs. One-way ANOVA with Tukey’s multiple comparisons test (e); two-Sided Spearman’s correlation (b,d,f,g); or Pearson’s correlation (c). Biological replicates represent individual patients, with exact numbers listed in each panel. NS, not significant (P ≥ 0.05).