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Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for
Hui Wang1,2, Jirui Li3, Yinghai Wang4
1Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Background:
Our previous research highlighted the potential role of immunoglobulin G4 (IgG4) in mediating immunosuppression within the tumor microenvironment (TME). Tertiary lymphoid structures (TLS) in the TME have important immune-related functions. This study aims to analyze the distribution characteristics of IgG4-expressing cells, regulatory T cells (Tregs), and M2-type macrophages as well as to elucidate the relationship between IgG4 and the polarization of M2 macrophages within TLS in esophageal cancer.
Object:
To elucidate the distribution of IgG4, Treg cells, and M2 macrophages in TLS and to assess the impact of IgG4 on macrophage polarization.
Methods:
Esophageal cancer tissue were analyzed with multiplex immunofluorescence to determine the spatial distribution and density of B cells, T cells, and their subtypes. The relationship between IgG4 and CD8+ T cells in TLS, along with interleukin-10 (IL-10) expression and Treg presence, was studied. Serum IgG4 and IL-10 levels were compared between patients and healthy controls. In vitro, the impact of IgG4 on monocyte differentiation into M2 macrophages was observed.
Results:
IgG4 density was inversely related with CD8+ T cells in mature TLS indicating a potential immunosuppressive role (P<0.05,*). Serum analysis revealed that both IgG4 (P<0.01, **) and IL-10 (P<0.0001, ****) were significantly elevated and positively correlated in tumor patients compared to controls (P<0.01, **). In vitro experiments confirmed that IgG4 monocyte differentiation into M2 macrophages, potentially enhancing the immunosuppressive phenotype in TLS.
Conclusion:
IgG4 and IL-10 may contribute to immunosuppression in esophageal cancer by promoting the polarization of M2 macrophages within TLS, which could be a therapeutic target.
