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IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression

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机构: [1]Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China. [2]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. [3]Provincial Key Laboratory of Molecular Pathology and Personalized Medicine Center of Collaborative and Creative Center, Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou, Guangdong, China. [4]Department of Gynecology, Peking University Cancer Hospital Yunnan, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China. [5]Jinxin Research Institute for Reproductive Medicine and Genetics, Xinan Hospital for Maternal and Child Health Care, Chengdu, China.
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关键词: immunoglobulin G4 tertiary lymphoid structure tumor microenvironment macrophage polarization interleukin-10

摘要:
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.To elucidate the distribution of IgG4, Treg cells, and M2 macrophages in TLS and to assess the impact of IgG4 on macrophage polarization.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.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.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.Copyright © 2025 Wang, Li, Wang, Chen, Zhang, Pan, Su, Li, Wang and Gu.

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大类 | 2 区 医学
小类 | 2 区 免疫学
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Q1 IMMUNOLOGY

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第一作者机构: [1]Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China. [2]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
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通讯机构: [1]Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China. [2]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. [3]Provincial Key Laboratory of Molecular Pathology and Personalized Medicine Center of Collaborative and Creative Center, Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou, Guangdong, China. [5]Jinxin Research Institute for Reproductive Medicine and Genetics, Xinan Hospital for Maternal and Child Health Care, Chengdu, China.
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