Intriguingly, the TME, especially in highly immune-active HBV-related HCC tumors, appears to dynamically regulate TAM PD-L1 expression by several stimuli including cytokines like IL-10 and IL-27, signaling pathways such as TGF-β/PKM2, and classical M1 macrophage activation involving TNF-α/NFkB and MAPK pathways (74, 162). This evidence concerns the gene TNF and hepatocellular carcinoma.