Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells

Figure 2 Mechanisms involved in hepatocellular carcinoma immune evasion. In physiological conditions, liver has the ability to induce immunotolerance against antigen from gastrointestinal tract. These mechanisms have a detrimental role during hepatocellular carcinoma development and progression. Upregulation of inhibitory programmed death-ligand 1 molecule from tumor cells, Kupffer cells, liver sinusoidal endothelial cells and antigen presenting cells, together with the release of interleukin-10 and transforming growth factor beta, lead to an exhausted phenotype of CD8+ cells and prevent tumor cells from immune damage. HCC: Hepatocellular carcinoma; PD-L1: Programmed death-ligand 1; CTL4A: Cytotoxic T lymphocyte antigen 4; PD-1: Programmed cell death protein 1; TGFβ: Transforming growth factor beta; IL-10: Interleukin-10.