Fig. 8: PARP14 is a negative feedback regulator of IFNγ signalling. | Nature Communications

Fig. 8: PARP14 is a negative feedback regulator of IFNγ signalling.

From: PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models

Fig. 8

A Chronic IFNγ pre-treated A375, 501-Mel, MC38, or YUMM2.1 cells were treated for 48 h with PARP14 pharmacological inhibitors RBN012759 (left) and RBN012811 (right). Expression of PARP14, pSTAT1, STAT1 and STAT1 target proteins is shown by western blot, with GAPDH visualised as a loading reference. B–C Graphs showing the relative maximum observed change in cell number as determined by crystal violet following 48 h treatment with varying concentrations of PARP14 inhibitor (12759: n = 9 per concentration; 12811: n = 9 per concentration) without IFNγ (B) or with 2-week IFNγ (C). The data were presented as mean ± S.E.M. D GSEA based on RNA-seq data depicting hallmark processes enriched in chronic IFNγ pre-treated tumours treated with RBN012759 or RBN012811 versus control (DMSO). The circle area depicts the NES, and colour intensity depicts the FDR, with ≤0.25 classed as significant. E RT-qPCR analysis of Cxcl10 and Cxcl11 mRNA expression levels in IFN-γ-YUMM2.1 and IFN-γ-MC38 cells treated with DMSO (n = 3); 12759 (n = 3); 12811 (n = 3). The data were presented as mean ± S.E.M. and the adjusted p-values were assessed by one-way ANOVA Dunnett’s test. Source data are provided as a Source Data file.

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