Fig. 3

Fig. 3

IL-6 in CAF conditioned media drives gene expression in ILC cells. (A) SUM44PE ILC cells were stimulated for 24 h with CAF-CM from ED26 ILC CAFs +/- IL-6 neutralizing antibody (1 µg/mL). Heatmap showing unbiased hierarchical clustering of the 110 differentially expressed genes determined by a generalized linear model likelihood ratio ANOVA-like test, FDR < 0.05. (B) Significantly enriched Hallmark gene sets in control (blue) and conditioned media treated samples (purple), FDR < 0.05 and, (C) CAF-CM stimulated cells (purple bars) were compared to CAF-CM + anti-IL-6 stimulated cells (green bars), FDR < 0.05. (D) Heatmap of the 43 genes in the CAF induced IL-6-dependent gene signature (CAF-IL6GS) from the RNA-Seq dataset. (E) CAF-IL6GS score calculated by ssGSVA in ER + NST (n = 427) and ER + ILC (n = 132) tumors in TCGA, Mann-Whitney test p = 0.0154 using GraphPad Prism. CAF-IL6GS score positively and significantly correlates with, (F) IL6 expression, (G) Hallmark IL6-JAK-STAT3 gene signature (n = 132) and, (H) ESTIMATE stromal score (n = 111) in ER + ILC tumors, Spearman correlation, * p < 0.05, *** p < 0.001, **** p < 0.0001 carried out using GraphPad Prism