Fig. 8: Combined targeting SPAK and PD-1 showed enhanced efficacy in HCC.

a Representative tissue region maps and expression analysis of SPAK levels from a spatial transcriptome dataset of ICI responders and non-responders (Mendeley Data: skrx2fz79n). b Representative abdominal MRI images, representative IHC staining and quantitative IHC analysis of SPAK levels performed on human HCC tissue obtained before and after treatment of ICI responders (n = 7 patients) and non-responders (n = 12 patients) (scale bars, 100 μm). c A schematic representation of the treatment strategy in the DEN/CCl4-induced HCC model. d, e Gross images of livers (scale bars, 5 mm), representative H&E staining (scale bars, 1000 μm), and tumor burden (n = 5 mice) from the indicated DEN/CCl4-induced HCC model. f A schematic representation of the treatment strategy in the AKT/NRasV12-induced HCC model. g, h Gross images of livers (scale bars, 5 mm), representative H&E staining (scale bars, 1000 μm), and tumor burden (n = 5 mice) from the indicated AKT/NRasV12-induced HCC model. i A schematic representation of the treatment strategy in the Hepa1-6-induced HCC model. j, k Gross images of livers (scale bars, 5 mm), representative H&E staining (scale bars, 200 μm), and tumor burden (n = 6 mice) from the indicated Hepa1-6-induced HCC model. l, m Total flux curve and bioluminescence images of mice from the indicated Hepa1-6-induced HCC model for the indicated days (n = 6 mice); a, b, e, h, k, m P values were calculated using an unpaired t test (two-tailed). The box plots show data distribution with the overlaid box plot indicating the median, first (Q1) and third (Q3) quartiles, and the whiskers extending to the 1.5× interquartile range (IQR). Source data are provided as a Source Data file.