Although direct clinical data in HCC are limited, preclinical and translational studies indicate that β-catenin activation is associated with T-cell exclusion and primary resistance to PD-1/PD-L1 inhibitors; therefore, PYGO2 loss could theoretically mitigate Wnt signaling output, while PYGO2 overexpression may contribute to immune evasion. Here, PYGO2 is linked to hepatocellular carcinoma.