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Figure 2. Alteration of immune cells in HBV- and NAFLD- HCC and corresponding immunotherapies. In HBV-infected liver microenvironment, MDSCs are recruited and macrophages are educated to polarization of pro-tumor phenotype, which constitute immunosuppressive microenvironment. However, excessive lipid accumulation and lipotoxic hepatocytes induce macrophages to pro-inflammatory phenotype which promotes liver damage. In both etiologies- associated HCC, cytotoxic T cells and NK cells inhibit progression of tumor formation through cytokines secretion or phenotype switch. B cells control progression of HBV infection by antibodies production and cytokines secretion, whereas promote NAFLD development towards fibrosis via inducing CD4⁺ T cells. Overall, activation and function of effector immune cells are suppressed by MDSCs and macrophages through interaction of checkpoint molecules, such as PD-1, PD-L1, CTLA-4, TIM-3 and LAG-3. Furthermore, several drugs blocking inhibitory checkpoint receptors have been developed and approved for treatment of cancer diseases. Collaboratively, CAR-T and CAR-NK cell therapy are investigated to be promising in treatment of liver cancer. HBV: hepatitis B virus; NAFLD: nonalcoholic fatty liver disease; HCC: hepatocellular carcinoma; MDSCs: myeloid-derived suppressor cells; CAR: chimeric antigen receptor; NK: natural killer; Mφ: macrophage; Arg1: arginase 1; MMP9: matrix metallopeptidase 9; IL: interleukin; IFN: interferon; TNF-α: tumor necrosis factor-alpha; TCR: T-cell receptor; BCR: B-cell receptor