Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Figure 1 Immune activation in the tumor microenvironment. Interaction between tumor cells and the immune system is demonstrated in this figure. Antigen presentation by dendritic cells (antigen presenting cells) leads to activation of cytotoxic T lymphocytes which eventually leads to death of tumor cells by the release of granzymes and perforins. Activation of cytotoxic T cells require additional co-stimulatory signals during the interaction between dendritic cells and cytotoxic CD8⁺ T lymphocytes. PD-1: Programmed death receptor-1; PD-L1: Programmed death receptor ligand-1; ICI: Immune checkpoint inhibitor; TCR: T-cell receptor; MHC-1: Major histocompatibility complex I.

Figure 2 Immune suppression in the tumor microenvironment. An immunosuppressive environment is brought about by the interaction of various immune cells in the tumor microenvironment (TME). N2 pro-tumorigenic tumor associated neutrophils (TANs) influence Tregs and T cells by various chemokines such as CCL-2, CCL-17 and interleukin (IL)-8, tumor necrosis factor, respectively. M2 tumor associated macrophages modulate the TME by influencing Tregs, natural killer (NK) cells and T lymphocytes through IL-6, vascular endothelial growth factor and IL-10, respectively. M type myeloid derived suppressor cells inhibit the NK cells and influence Tregs through IL-6. Cancer associated fibroblasts modulate the effect of N2 TANs via IL-6. Dendritic cells also play a role in the TME by regulating Tregs. CAFs: Cancer associated fibroblasts; PD-1: Programmed death receptor-1; PD-L1: programmed death receptor ligand-1; pDC: Dendritic cell; M-MDSC: Monocytic myeloid derived suppressor cells; NK cell: Natural killer cell; VEGF: Vascular endothelial growth factor; TAN: Tumor associated neutrophils; TAM: Tumor associated macrophages; Tregs: Regulatory T cells; IL: Interleukin.

Figure 3 Tumor microenvironment balance. Depicted is the inclination of the tumor microenvironment towards an immunosuppressive environment and its components. NK cell: Natural killer cell; TAN: Tumor associated neutrophils; TAM: Tumor associated macrophages; Treg: Regulatory T cells; MDSC: Myeloid derived suppressor cells; TME: Tumor microenvironment.