Fig. 3

Cirrhotic-ECM orchestrated a neutrophils/NETs-dominant immune-suppressive TME through Col1. A Chord plot of KEGG enrichment based on DEGs from patients with ECM score -high and -low in TCGA-LIHC cohort. B Representative images and quantification of IHC and multiplex fluorenes staining of MPO and H3cit in HCC patient with fibrosis. Scale Bar: 50 μm. C Establishment scheme of Hepa1-6 orthotopic HCC model in C57BL/6 mice w/o DMN-induced cirrhotic-ECM alteration. D, E Representative IHC staining (D) and quantification (E) of the MPO (neutrophils) and CD8 (T cells) in orthotopic model in C. Scale Bar: 100 μm. F, G Representative multiplex fluorenes staining (F) and quantification (G) of the MPO+H3cit (NETs) in orthotopic model in C. Scale Bar: 100 μm. H Establishment scheme of Hepa1-6 subcutaneous HCC model in C57BL/6 mice w/o Col1 co-injection. I, J Representative flow cytometry images (I) and quantification (J) of the Gr1+Ly6zG+ neutrophils and CD3+ T cells in subcutaneous model in H. K, L Representative multiplex fluorenes staining (K) and quantification (L) of the MPO + H3cit (NETs) in subcutaneous model in H. Scale Bar: 20 μm. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001