CD8A and hepatocellular carcinoma: This is evidenced by the expression of IRG1 in TAMs of human and mouse tumors, by cell (co)culture studies demonstrating that tumor cells or tumor-secreted factors induce IRG1 expression through NF-κB activation, by genetic studies in mice showing that deletion of Irg1 in TAMs reduces tumor growth and enhances the efficacy of PD-1/PD-L1 blockade, and by human data showing a negative correlation of IRG1 expression with tumor-infiltrating CD8+ T cells and HCC patient response to immunotherapy.