Fig. 7

Targeting VCP combined with anti-PD1 modulates the TME of HCC. a Treatment schema of Hepa1-6 tumor-bearing C57BL/6 mice. Schematic created with BioRender.com. b Hepa1-6 tumors were dissected from the C57BL/6 mice treated with vehicle, CB-5083, aPD1, or both (n = 6/group). c Data from (b). d–f The percentage of CD8⁺T cells, cytokines production (Granzyme B, IFN-γ), and activation indicators (CD69, CD25, CD44) in Hepa1-6 tumors were measured by flow cytometry analysis (n = 5/group). g, h Bioluminescence images of conditional knockout mice at indicated time points after plasmid injection. Bioluminescence signal at indicated time points post plasmid injection in Vcp conditional knockout mice. i Kaplan–Meier survival curve of conditional knockout mice treated as in (g). Log-rank test. j–l The percentage of CD8⁺T cells, cytokines production (Granzyme B, IFN-γ), and activation indicators (CD69, CD25, CD44) with spontaneous tumors in Vcp conditional knockout mice were measured by flow cytometry (n = 5/group). m Spontaneous tumor sections of conditional knockout mice were stained with multiple immunofluorescence. n Schematic summary graph of the main conclusion of the study. Tumor cells VCP promotes the generation of G3P through stabilizing GPD1L, which then impairs TCR signaling and causes CD8⁺T cells dysfunction. Schematic created with BioRender.com. Data are presented as mean values ± SD. Statistical significance was determined using two-sided t-tests, *P < 0.05, **P < 0.01, and ***P < 0.001