Fig. 5: The combinational treatment of PDAC with PCAF inhibitor and anti-PD-1 monoclonal antibody.

A A schematic diagram showing the subcutaneous tumor model (n = 6 mice per group in one experiment, 6 × 10⁶ PANC02 cells per mouse) treated with bromosporine and anti-PD-1 antibody. B. The tumor volume growth curves of subcutaneous tumors from (A). C, D Image and weights of the subcutaneous tumors at the end point of experiments (n = 6 mice per group). E The statistical analysis of the cell ratio of tumor-infiltrating neutrophils and CD8⁺ T cells isolated from subcutaneous tumors (n = 3 mice per group). F Western blot analysis demonstrates H3K18la levels in the subcutaneous tumors (n = 3 biologically independent samples per group) from (A). Histone H3 and H3K18la blots are from parallel-processed separate gels (size conflict) with samples from the same experiment. G Relative serum CXCL1 levels in mice treated with or without bromosporine/anti-PD-1 antibody were measured by ELISA (n = 6 mice per group). H A schematic diagram showing the combinational treatment schedule for the orthotopic KPC-luc tumor model (n = 21 mice per group in one experiment, 2 × 10⁶ KPC-luc cells per mouse). I, J Image and weights of the orthotopic tumors at the end point of experiments (n = 6 mice per group). K–N Tumor-infiltrating neutrophils, CD8⁺ T cells, GZMB⁺CD8⁺ T cells, and PD-1⁺CD8⁺ T cells were analyzed using flow cytometry. Representative graphs of flow cytometry (left panel) and statistical analysis of the cell ratio (right panel) (n = 6 mice per group). O Western blot analysis showing the H3K18la levels in the orthotopic tumors (n = 3 biologically independent samples per group) from (H). Histone H3 and H3K18la blots are from parallel-processed separate gels (size conflict) with samples from the same experiment. P Representative luminescence images and Quantification of radiance intensity of the mouse model in (H). Q Survival probability of mice with orthotopically transplanted PDAC (n = 15 mice per group). R A working model displaying the signaling pathway through which the aerobic glycolysis-mediated Lactate-PCAF-H3K18la-CXCL1 axis modulates the tumor microenvironment in pancreatic cancer, and the scientific basis for the development of a novel therapeutic strategy for PDAC. Data represent mean ± SEM. Statistical analysis was conducted using the two-tailed unpaired Student’s t test (B, D, E, G, J–N, P) and the log-rank test (Q). Source data are provided as a Source Data file.