Skip to main content
. 2022 Jan 24;71(11):2266–2283. doi: 10.1136/gutjnl-2021-324834

Figure 7.

Figure 7

TAK-981 reduces KPC3 growth in a CD8 T cells and IFNAR dependent manner. (A) Western blot analysis of STAT1 phosphorylation (pSTAT1) in splenocytes obtained from C57BL/6 mice treated ex vivo with 150 nM TAK-981 in the presence of IFNAR1 blocking or IFN-γ neutralising antibodies (n=3). (B) Western blot analysis showing STAT1 phosphorylation (pSTAT1) in CD8 T cells from Pmel-1 TCR transgenic mice ex vivo treated with 150 nM TAK-981or DMSO control for the indicated time points (n=2). (C) qPCR analysis showing the expression of IFN-stimulate genes and interferons in mouse CD8 T cells treated ex vivo with 150 nM TAK-981 for the indicated time points. Statistical testing was performed using two way ANOVA with Dunnett’s multiple comparisons test. Data are expressed as mean±SEM *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. (D) Experimental strategy. KPC3 tumours were subcutaneously transplanted in C57BL/6 mice (n=8 mice per group). When tumours were palpable, mice were treated with vehicle or 7.5 mg/kg TAK-981 twice weekly (days 0, 3, 7, 11) and the indicated antibodies. (E) C57BL/6 mice bearing subcutaneous KCP3 tumours were treated with CD8 neutralising or isotype control antibody on days −3 and −1 via intraperitoneal injection. CD8 depletion was confirmed prior to TAK-981 treatment. Tumour-bearing mice were treated with 7.5 mg/kg TAK-981 on days 0, 3, 7, 11 and anti-CD8 or isotype control on days 2, 6 and 10. Data are shown as mean as mean±SEM, n=8 mice per group. Tumour growth was compared using two-way ANOVA (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001) with Dunnett’s multiple comparisons test. (F, G) C57BL/6 mice bearing subcutaneous KCP3 tumours were treated with 7.5 mg/kg TAK-981 on days 0, 3, 7, 11, and (F) anti-IFNAR1 or isotype control antibodies, or (G) anti-IFN-γ or isotype control antibodies were administered via intraperitoneal injection on days (−1, 2, 6, 10). Data are shown as mean as mean±SEM, n=8 mice per group. Tumour growth was compared using two-way ANOVA (p<0.05; **p<0.01; ***p<0.001; ****p<0.0001) with Dunnett’s multiple comparisons test. ANOVA, analysis of variance; PDAC, pancreatic ductal adenocarcinoma.