FIGURE 3.

Dynamic phenotypic transition of TAMs during liver cancer progression. (A) KCs are unique macrophages in the liver and are part of the mononuclear phagocyte system. Those KCs in the liver sinusoids can phagocytize foreign antigens, antigen‐antibody complexes, and cell debris and also secrete cytokines, which is unfavorable for cancer initiation. DCs and HSCs present in the space of Disse cooperate with other immune cells such as KCs to maintain the liver immune microenvironment. (B) The immune microenvironment of liver cancer (HCC or iCCA) is constantly changing. The resident macrophages inside the tumor can alter their phenotype following stimulation. Furthermore, numerous circulating monocytes in the peripheral blood, including Tie⁺ monocytes, are recruited to the tumor milieu. Prior to converting pro‐tumoral TAMs, CD11b and Ly6C are highly expressed, while F4/80 is low. Nevertheless, TAMs, which suppresses the immune response, have higher F4/80 and lower CD11b and Ly6C levels of expression. HSCs in the space of Disse are also activated and may synergize with TAMs to promote liver cancer progression. Abbreviations: KCs, Kupffer cells; DCs, dendritic cells; HSCs, hepatic stellate cells; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma; Clec4F, C‐type lectin domain family 4 member F; Tim‐4, T‐cell immunoglobulin and mucin domain‐containing 4; CX3CR, C‐X3‐C motif chemokine receptor; CSF1R, colony‐stimulating factor 1 receptor; CCR2, C‐C motif chemokine receptor 2; MHC‐II, major histocompatibility complex class II; GATA, glutamyl‐tRNA amidotransferase, subunit A; MoMFs, monocyte‐derived macrophages; MACRO, macrophage receptor with collagenous