Fig. 4: PGE₂ and IFN-I responses determine myeloid cell abundance and their functional inflammatory state in the TME.

a, UMAP of scRNA-seq of CD45⁺ cells in YUMM1.7^OVA R^TT Ptgs1/2 KO and R^TT IRF3/7 tumours 72 h after ACT (n = 3 tumours pooled per group). See Fig. 1c for cell cluster annotation. b, Scoring of the TME-COX and TME-IRF3/7 signatures (Supplementary Table 4) in myeloid fractions of responder (n = 6) and non-responder (n = 7) patients before TIL infusion⁴³. c, Scoring of an ISG signature³⁷ in the scRNA-seq from a. d, Flow cytometry quantification of myeloid populations normalized to the CD45⁺ fraction from YUMM1.7^OVA N^TT tumours in Rag2^–/– mice treated with anti-IFNAR1 or anti-IFNγ (n = 5 tumours per group, except n = 4 in anti-IFNAR1 + ACT and ant-IFNγ + ACT). e, RNA velocity of the MoMac compartment from R^TT Ptgs1/2 KO tumours. f, Representative contour plots of Ly6C⁺ monocytes depicting Ly6A expression 72 h after i.t. transfer into N^TT and R^TT tumours in Rag2^–/– mice (n = 5 tumours per group). g, Left, BLI quantification of T cells 96 h after ACT of YUMM1.7^OVA R^TT cells into Cd11c^cre-Ptger2^–/–Ptger4^fl/fl mice (EP2/EP4 KO) or Cd11c^cre (CTRL) mice (n = 7 mice per CTRL group and n = 8 mice per EP2/EP4 KO group); two-tailed Mann–Whitney U-test. Right, representative BLI image (key as in Fig. 1b). h, Representative contour plots of Ly6C⁺ monocytes depicting expression of Ly6A 48 h after treatment with CM from cancer cells with or without a COX1/2i (indomethacin) and with or without anti-ΙFNAR1 or isotype (n = 3 biological replicates). i, Heatmap of scaled ISG expression in BMDCs exposed to CM from N^TT or R^TT cells and with or without a COX1/2i in the presence of anti-ΙFNAR1 or isotype (n = 4 technical replicates) measured by RT–qPCR. j, Heatmap of scaled ISG expression in BMDCs treated with IFNβ and PGE₂ measured by RT–qPCR (n = 4 technical replicates). Bar graphs depict the mean ± s.e.m.

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