Mutations of genes in important signal transduction pathways—such as the Wnt/β-catenin pathway, which is altered by mutations in many human cancers72and especially prevalent in HCC73—can also impact the TME and increase the probability of immune evasion of the tumor contributing to primary resistance.74Upregulated β-catenin increases PD-L1 expression with a subsequent reduction of cytotoxicity of CTL, inhibition of DC and T cell recruitment, and enhanced immunosuppression by Treg. This evidence concerns the gene CD274 and neoplasm.