fig2

Figure 2. Function of M1 and M2 subsets of liver macrophages. Although this classification is considered obsolete, as several novel functional subsets have been described, it remains the best studied to date. M1 cells are the origin of TAM1, which are pro-inflammatory and anti-tumoral and promote apoptosis and phagocytosis of HCC cells. Moreover, they recruit and activate killer immune cells such as NK cells and effector CD8+Tcells. On the other hand, M2 cells are the origin of TAM2 cells that are pro-tumoral and favor HCC proliferation and metastasis. Moreover, they cause exhaustion of CD8+T cells and increase the proportion of T reg cells. All subsets of M2 cells (M2a-M2d) also favor tumor development. BMDMF: Bone marrow-derived macrophage; EmKC: embryonically derived Kupffer cell; SAM: scar-associated macrophage; M1: classically activated macrophage; M2: alternatively activated macrophage; M2a-M2d: M2 macrophage subsets; TAM: tumor-associated macrophage; TAM1: M1-like tumor-associated macrophage; TAM2: M2-like tumor-associated macrophage; HCC: hepatocellular carcinoma; NK: natural killer cell; CD8+ T: CD8-positive T lymphocyte; Treg: regulatory T cell; IL: interleukin; IL-1α: interleukin-1 alpha; IL-1β: interleukin-1 beta; IL-4: interleukin-4; IL-6: interleukin-6; IL-10: interleukin-10; IL-12: interleukin-12; IL-13: interleukin-13; IL-17A: interleukin-17A; IL-18: interleukin-18; IL-23: interleukin-23; IL-37: interleukin-37; TNFα: tumor necrosis factor alpha; IFNγ: interferon gamma; TGFβ: transforming growth factor beta; GM-CSF: granulocyte-macrophage colony-stimulating factor; PGE2: prostaglandin E2; ROS: reactive oxygen species; NOS: nitric oxide synthase; LPS: lipopolysaccharide; PD-1: programmed cell death protein 1; PD-L1: programmed death-ligand 1; TIM-3: T-cell immunoglobulin and mucin-domain containing-3.