Fig. 6: HBV-related HCC tumor infiltrating MDK^highIFN-γ^lowCD8⁺ T cells displayed a dysfunctional immunosuppressive phenotype.

A Violin plots indicating expression of exhausted genes in CD8⁺ T cells (LAG3, CTLA4, and CXCL13) (top panel) or cytotoxic genes (GZMA, PRF1, and IFNG) (middle panel) in HBV (blue) and non-HBV (green) tumor samples, violin plots depicting the expression of LAG3, CTLA4, CXCL13 and IFNG in HBV (blue) and non-HBV (green) samples from the Validation cohort 2 (bottom panel). B Violin plot indicating the cytotoxic and exhausted average scores of CD8⁺ T cells in HBV(blue) and non-HBV (green) tumor samples in the discovery (left panel) and validation cohort 2 (right panel). C The volcano plot shows differentially expressed genes between HBV (red dots) and non-HBV tumor-infiltrated CD8⁺ T cells (blue dots). The names of the most significant genes are indicated in the plot. D Violin plot indicating the expression of cytotoxic marker genes in IFNG^high (log₂ expression>0.585) and IFNG^low (log₂ expression_<0.585) CD8⁺ T cells across HBV and non-HBV tumor samples. E Representative IHC staining, showing CD8⁺IFNG⁺ T cells in paired HBV and non-HBV-HCC samples. Scale bar, 20 μm. F Violin plots indicating the expression of MDK cells in HBV (blue) and non-HBV (green) tumor samples in the discovery cohort (left panel) and validation cohort 2 (right panel). G The Kaplan-Meier plot of disease-free survival in the TCGA LIHC cohort compares low versus high MDK^high (signature of top 50 genes) in hepatitis virus HCC patients. The plot indicates the number of patients from each subgroup, the Log-Rank t-test results, and the number of patients (N). H The Kaplan-Meier plot of disease-free survival in the TCGA database compares low versus high MDK in Hepatitis (left panel) and non-hepatitis virus (right panel) HCC patients. The plot shows patient numbers from each subgroup, the Log-Rank t-test results, and the number of patients (N). I Violin plot indicating the expression of exhausted (upper panel) and cytotoxic marker genes(lower panel) in CTLA4^high (log₂ expression>0.585) and CTLA4^low (log₂ expression<0.585) CD8⁺ T cells across HBV and non-HBV tumor samples. J Violin plots showing the average score of cytotoxic and exhausted signals in CTLA4^high (log₂ expression>0.585) and CTLA4^low (log₂ expression<0.585) CD8⁺ T cells across HBV and non-HBV tumor samples in both the discovery cohort (left panel) and the validation cohort 2(right panel). The p-values in (A, B, D, F, I, and J) were calculated using Student’s t-test. All statistical comparisons were performed on biologically independent samples (n = 5 HBV-HCC and n = 3 non-HBV-HCC) from both the discovery and validation cohort 2. See also Supplementary Fig. 12.