Extended Data Fig. 3: Anti-PDL1 treatment does not achieve anti-tumour effects in NASH-induced tumours, but in non-NASH livers PD1-targeted immunotherapy leads to prolonged survival.
From: NASH limits anti-tumour surveillance in immunotherapy-treated HCC
a, MRI images of livers of mice after 13 months CD-HFD either untreated or after 7 weeks of treatment with anti-PDL1 antibodies (CD-HFD n = 6 mice; CD-HFD + anti-PDL1 n = 8 mice). Dashed outlines indicate tumour nodules. Scale bar, 10 mm. b, Livers of mice fed with ND or CD-HFD for 13 months and either untreated or treated for 8 weeks with anti-PDL1 antibodies. Arrowheads, tumours or lesions. Scale bar, 10 mm. c, Body weight and ALT of mice as in b (ND n = 8 mice; CD-HFD n = 6 mice; CD-HFD + anti-PDL1 n = 6 mice). d, e, NAS evaluation by H&E, quantification of fibrosis by Sirius Red, and quantification of CD8, PD1 and PDL1 staining of hepatic tissue by immunohistochemistry (d) and corresponding micrographs (e) of mice fed for 13 months with ND or CD-HFD and untreated or treated for 8 weeks with anti-PDL1 antibodies (NAS: ND n = 7 mice; CD-HFD n = 6 mice; CD-HFD + anti-PDL1 n = 6 mice; Sirius Red: ND n = 7 mice; CD-HFD n = 5 mice; CD-HFD + anti-PDL1 n = 6 mice; CD8: ND n = 5 mice; CD-HFD n = 5 mice; CD-HFD + anti-PDL1 n = 5 mice; PD1 and PDL1: ND n = 5 mice; CD-HFD n = 5 mice; CD-HFD + anti-PDL1 n = 6 mice). Scale bar, 100 μm. Arrowheads, positive cells. f, Tumour or lesion incidence in mice fed with CD-HFD for 15 months and untreated or treated for 8 weeks with anti-PDL1 antibodies (CD-HFD n = 19 tumours/lesions in 25 mice; CD-HFD + anti-PDL1 n = 7 tumours/lesions in 8 mice). g, Survival analysis of mice with hydrodynamically delivered NrasG12Vp19Arf−/− liver tumours with OVA as antigen, treated with isotype or anti-PD1 antibodies (control n = 8 mice; anti-PD1 n = 10 mice). h, Survival analysis of a non-NASH model of HCC in which tumours are generated autochthonally in the liver by hydrodynamic injection of genetic elements (OVA, SIY, SIN and MYC-lucOS, in a CRISPR-based vector with tumour suppressor p53 deleted (sg-p53), and a transposase-expressing vector (SB13)). Mice were treated on days 7, 9 and 11 with IgG or anti-PD1 (control n = 6 mice; anti-PD1 n = 6 mice). i, Survival analysis of mice with RIL-175 Hras/P53-mutant hydrodynamically induced liver tumours, treated with IgG or anti-PD1 (n = 35 mice per group). All data are shown as mean ± s.e.m. c, d, One-way ANOVA and Fisher’s LSD test. f, Two-sided Fisher’s exact test. i, Two-tailed Student’s t-test. g–i, Two-sided χ2 test.
