Mutations or activation of pathways such as CTNNB1/WNT-β-catenin, TGF-β, MYC, TP53, ARID1A, and CDK20 exert profound effects on immune responses and immune cell recruitment.4,515 For example, CTNNB1 mutations diminish CCL5 expression, impairing dendritic cell (DC) recruitment, and reducing NKG2D ligand expression, thus hindering natural killer (NK) cell-mediated responses.516,517 About a quarter of HCC harbor β-catenin mutations, correlating with reduced lymphocyte infiltration and potential resistance to PD-1 blockade, although clinical validation is needed. This evidence concerns the gene TGFB1 and hepatocellular carcinoma.