IFN-γ secreted by CD8+T cells induced PD-L1 expression on hepatoma cells, which in turn promoted CD8+T cell apoptosis in vitro.47 Hepatic stellate cells isolated from hematocellular carcinoma expressed high levels of PD-L1, which was associated with enhanced T-cell apoptosis.48 These findings suggest that the advanced stage of T-cell exhaustion is the physical deletion (Figure 1). The gene discussed is CD8A; the disease is hepatocellular carcinoma.