Figure 4. IL-1-induced CAF secretion of CXCR1/2 ligands is suppressed by IL1RAP blockage. (A) RNA expression of genes encoding chemokines in CAF and BxPC-3 co-cultures treated with nadunolimab or isotype control (average of N=4 with boxes showing minimum and maximum values; data from the RNA sequencing experiment are presented in figure 3). (B) Concentration of corresponding chemokines in the media from CAF and BxPC-3 co-cultures treated with nadunolimab or isotype control. The full data set is shown in online supplemental figure S4A. (C) CXCL1, CXCL5 and CXCL6 levels in media after 24 hours culture of CAFs, stimulated with 0.1 ng/mL IL-1α and IL-1β in combination with nadunolimab or isotype control (20 µg/mL). (D) Expression of CXCL chemokines in normal pancreas (N=167) and PDAC tumors (N=150) in the GTEx and TCGA data sets. Significance is calculated by one-way ANOVA test with Šidák correction in (A–C) and by Mann-Whitney test in (D). Mean values in A to C are shown with N=3-6. Significance levels are indicated as *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. ANOVA, analysis of variance; CAF, cancer-associated fibroblast. FPKM, fragments per million; PDAC, pancreatic ductal adenocarcinoma; ns, not significant. TPM, transcripts per million.