Extended Data Fig. 4: Elicitation of the IL-1β+ TAM state by PGE2 and TNF-α.
From: IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer
a, GSEA (GO BP) on genes ranked by correlation with absorption probability of the monocyte-to-Il1b+ TAM transition. Selected terms are shown. b, GSEA on genes ranked by log2FC between each mouse TAM subset versus other TAMs. Gene sets: IL-1β-induced or TNF-α-induced genes. NES, Normalized Enrichment Score. c, Concentration (mean ± SEM) of TNF-α (n = 18) and IL-1β (n = 17) in plasma and tumor of PDAC patients (n = 12). ***p < 0.001 ****p < 0.0001 (unpaired student’s two-tailed t test). d, Expression of IL-1β (intracellular staining) in mouse BMDMs treated for 6 h with IL-1β or TNF-α. e, Quantification of PGE2 in human PDAC samples and control (Ctrl) matched normal adjacent tissue (n = 7/group) by mass spectrometry (left), or in culture supernatants of KPC (n = 14), KC (n = 10) and PANC02 (n = 3) PDAC cells by ELISA (mean±SD, right). *p < 0.05 (paired student’s two-tailed t test). f, GSEA (PGE2-induced genes) on genes ranked by log2FC between each mouse TAM subset versus other TAMs (orthotopic KPC). NES, Normalized Enrichment Score. g, Transcript (mean ± SD, left) or protein (intracellular staining, right) expression of IL-1β in BMDMs stimulated as indicated (n = 2). h, Expression (intracellular staining) of IL-1β in BMDMs (n = 6, left) or BM monocytes (n = 3, right) stimulated as indicated. ****p < 0.0001 (one-way ANOVA).