Neutrophils are pathogenic in MASH-related HCC. (A) Kaplan–Meier plots comparing HCC patients from various datasets with high (top 25%) and low (top 25%) TAN signature scores. (B) The etiologies of HCC patients in A. (C) Kaplan–Meier plots comparing different groups of TCGA-LIHC patients with high and low TAN signature scores. (D and E) Mice bearing NRAS/AKT or cMYC/sgp53 HCC tumors were sacrificed at 4 or 7 wk after tumor induction, respectively. Representative images of AFP staining (left) and neutral lipid staining (right) on liver sections. The scale bar represents 100 µm (D). Representative FACs plots and percentages of CD11b⁺Ly6G⁺ neutrophils among CD45⁺TILs (n = 4–5/group) (E). (F) NRAS/AKT HCC mice (top panel) and cMYC/sgp53 HCC mice (bottom panel) were treated with αLy6G or isotype control mAbs for 2 wk. Representative images of HCC livers (left); liver-to-body weight ratio (middle) and tumor nodule counts (right). Scale bar represents 1 cm. (G) Tumor volume of RIL175 orthotopic HCC mice fed with MCD diet (MCD + RIL175; top) or Chow diet (CD + RIL175; bottom), following αLy6G or isotype control mAb treatments. Each symbol represents one mouse. Data are mean ± SEM (E–G) and represent two to three independent experiments (D–G). *P < 0.05, ***P < 0.001 by Kaplan–Meier analysis (A and C) and unpaired Student’s t test (F and G). NA, not available; T, tumor; NT, non-tumor.