Supplementary Materials

The PDF file includes:

• Fig. S1. Selective HDAC8 inhibition attenuates orthotopic tumor growth in immunocompetent but not immunodeficient mice.
• Fig. S2. HDAC8 inhibition has limited effect on myeloid cell proportions.
• Fig. S3. Cytolytic molecule production by tumor-infiltrating CD8⁺ T cells.
• Fig. S4. Effect of HDAC8 inhibition on tumor cell apoptosis in immunocompetent and immunodeficient mice.
• Fig. S5. Effect of HDAC8 inhibition on tumor cell proliferation in immunocompetent and immunodeficient mice.
• Fig. S6. Intratumoral CD8/T_reg ratio determines the antitumor effect of HDAC8 inhibition.
• Fig. S7. Saturation analyses for sample number estimation.
• Fig. S8. Integrative analysis of the eight patients with NAFLD-HCC with HDAC8 overexpression.
• Fig. S9. Correlative expression analysis between HDAC8 and the 1251 enhancer-silenced genes.
• Fig. S10. Effects of HDAC8 inhibition on chemokine expressions in vitro and in vivo.
• Fig. S11. Expression of CCL4 protein in normal livers and tumors with or without HDAC8 inhibition.
• Fig. S12. Effect of CCL4 on tumor cell growth and T cell migration.
• Fig. S13. Knockdown of tumor-expressed HDAC8 has limited effects on CD8⁺ T cell proportions in dLN.
• Fig. S14. Effects of selective-HDAC8 and pan-HDAC inhibitors in vivo and in vitro.
• Fig. S15. Effects of HDAC8 and PD-L1 coblockade in a spontaneous NAFLD-HCC model.
• Fig. S16. A schematic diagram of this study.
• Table S1. Clinicopathological information of patients with NAFLD-HCC.
• Table S2. Primers used in this study.
• Table S3. Antibodies used in this study.

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Other Supplementary Material for this manuscript includes the following:

• Data file S1 (Microsoft Excel format). List of 1251 silenced enhancer-target gene pairs in human HCCs.
• Data file S2 (Microsoft Excel format). Original data.