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

Minni Zhang; Kun Liu; Qiuyue Zhang; Junnv Xu; Jinchen Liu; Haifeng Lin; Bo Lin; Mingyue Zhu; Mengsen Li

doi:10.3389/fimmu.2023.1081572

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

Front Immunol. 2023 Feb 23:14:1081572. doi: 10.3389/fimmu.2023.1081572. eCollection 2023.

Authors

Minni Zhang¹, Kun Liu¹, Qiuyue Zhang¹, Junnv Xu², Jinchen Liu¹, Haifeng Lin², Bo Lin¹, Mingyue Zhu¹, Mengsen Li^{1

2

3}

Affiliations

¹ Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Hiakou, Hainan, China.
² Department of Medical Oncology, Second Affiliated Hospital, Hainan Medical College, Haikou, Hainan, China.
³ Institution of Tumor, Hainan Medical College, Hiakou, Hainan, China.

Abstract

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.

Keywords: PI3K/AKT signaling; alpha-fetoprotein; immune escape; macrophage phagocytosis; macrophage polarization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / metabolism
Humans
Interferon-gamma / metabolism
Liver Neoplasms* / metabolism
Macrophages / metabolism
Phenotype
Phosphatidylinositol 3-Kinases / metabolism
alpha-Fetoproteins / genetics

Substances

alpha-Fetoproteins
Phosphatidylinositol 3-Kinases
Interferon-gamma

Grants and funding

This work was supported by the National Natural Science Foundation of China (Nos. 82060514 and 81960519), the Natural Science Foundation of Hainan Province (Nos. 820RC634, 2019CXTD406, 2019CR204, and 20168263), and the Research Project of Take off the Proclamation and Leadership of Hainan Medical College Natural Science Foundation(No. JBGS202106), and Hainan Provincial Science and Technology Special Fund(No. ZDYF2021SHF222), and Hainan Provincial Association for Science and Technology Program of Youth Science Talent and Academic Innovation (No. QCXM 201922).