Extended Data Fig. 7: Type I and type II IFNs determine the inflammatory state.

a, b, Overall survival of melanoma patients stratified according to the TME-COX and TME-IRF3/7 signatures (Supplementary Table 4) (left) and correlation of intratumoral CD8⁺ T cell signature (right) in the Gide et al. RNA-seq data-set⁴⁹. PCC=Pearson correlation coefficient. c, TME-COX and TME-IRF3/7 signatures projected on the myeloid UMAP from baseline tumors (split for responder and non-responders to TIL therapy) from the Barras et al.⁴³ patient cohort (above) and individual score across different myeloid populations (below). d, Gene set enrichment analysis (GSEA) of N^TT and R^TT tumors pre and post-ACT based on scRNA-seq analysis. Normalized enrichment score (NES). Multiple correction testing with false discovery rate. e, Pathway enrichment analysis of the top variable genes in the immune tumor microenvironment (TME) from N^TT and R^TT tumors pre and post-ACT analyzed by scRNA-seq. 1, 2 and 3 depict each gene cluster identified. Benjamini-Hochberg correction for multiple testing. f, TME characterization of YUMM1.7^OVA R^TT Ptgs2 KO tumors pre and 72 h post-ACT upon αIFN-γ and αIFNAR1 treatment (n = 5 tumors/group, except n = 4 for isotype and αIFNAR + ACT). g, Trajectory analysis and pseudotime of the MoMac compartment of YUMM1.7^OVA N^TT and R^TT tumors. h, Density plots of F4/80⁺ macrophages after exposure of BM-derived monocytes to PGE₂ for 48 h (left) and quantification (right) (n = 3 replicates per condition). i, Scheme outlining the intratumoral (i.tu.) transfer of CD45.1⁺ BM-derived monocytes into N^TT and R^TT tumors injected into CD45.2⁺ Rag2^−/− mice (left) and inflammatory monocytes frequencies 3 days after transfer (right) (n = 5 tumors/group). j, Scheme outlining the knockout of EP2 (Ptger2) and EP4 (Ptger4) in OT-1 T cells and i.v. injection into YUMM1.7^OVA R^TT tumor-bearing Rag2^−/− mice (left) and tumor growth (n = 6 mice/group) (right). Arrow indicates the day of ACT. k, Expression of Ptger2 and Ptger4 across populations from the YUMM1.7^OVA scRNA-seq. Bar graphs depict the mean ± s.e.m. Statistical analysis was performed with a two-tailed unpaired student’s t-test in h and i. p-value in a and b was calculated using a Cox’s proportional hazards model (survival) and with a two-sided Pearson’s correlation (correlations).

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