Alpha fetoprotein promotes polarization of macrophages towards M2-like phenotype and inhibits macrophages to phagocytize hepatoma cells

• DOI: 10.3389/fimmu.2023.1081572
• Publication Date: 2023-02-23T05:40:58Z
• Authors: Minni Zhang; Kun Liu; Qiuyue Zhang; Junnv Xu; Jinchen Liu; Haifeng Lin; Bo Lin; Mingyue Zhu; Mengsen Li
• Keywords: 0303 health sciences; Carcinoma, Hepatocellular; macrophage polarization; Macrophages; Immunology; Liver Neoplasms; immune escape; RC581-607; alpha-fetoprotein; Phosphatidylinositol 3-Kinases; Interferon-gamma; 03 medical and health sciences; macrophage phagocytosis; Phenotype; Humans; alpha-Fetoproteins; Immunologic diseases. Allergy; PI3K/AKT signaling

Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains unclear. In the present study, we explored the correlation between AFP regulation of macrophage function and the possible regulatory mechanisms. Human mononuclear leukemia cells (THP-1) and monocytes from healthy donors were used to analyze the effect of AFP on the macrophages’ phenotype and phagocytosis. THP-1 cells and healthy human donor-derived monocytes were polarized into M0 macrophages induced by phorbol ester (PMA), and M0 macrophages were polarized into M1 macrophages induced by lipopolysaccharide(LPS) and interferon-γ(IFN-γ). Interleukin-4(IL-4) and interleukin-13(IL-13) were used to induce M0 macrophage polarization into M2 macrophages. Tumor-derived AFP(tAFP) stimulated M0 macrophage polarization into M2 macrophages and inhibited M1 macrophages to phagocytize HCC cells. The role of AFP in promoting macrophage polarization into M2 macrophages and inhibiting the M1 macrophages to phagocytize HCC cells may be involved in activating the PI3K/Akt signaling pathway. AFP could also enhanced the migration ability of macrophages and inhibited the apoptosis of HCC cells when co-cultured with M1-like macrophages. AFP is a pivotal cytokine that inhibits macrophages to phagocytize HCC cells.