IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression
BackgroundOur 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 charac...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1497783/full |
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| author | Hui Wang Hui Wang Jirui Li Yinghai Wang Yang Chen Yang Chen Weifeng Zhang Xinyan Pan Xinyan Pan Chanjuan Su Ziteng Li Li Wang Li Wang Jiang Gu Jiang Gu |
| author_facet | Hui Wang Hui Wang Jirui Li Yinghai Wang Yang Chen Yang Chen Weifeng Zhang Xinyan Pan Xinyan Pan Chanjuan Su Ziteng Li Li Wang Li Wang Jiang Gu Jiang Gu |
| author_sort | Hui Wang |
| collection | DOAJ |
| description | BackgroundOur 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.ObjectTo elucidate the distribution of IgG4, Treg cells, and M2 macrophages in TLS and to assess the impact of IgG4 on macrophage polarization.MethodsEsophageal 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.ResultsIgG4 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.ConclusionIgG4 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. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-91288e84d86c48dfb545751acc3ad8342025-01-17T06:51:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14977831497783IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppressionHui Wang0Hui Wang1Jirui Li2Yinghai Wang3Yang Chen4Yang Chen5Weifeng Zhang6Xinyan Pan7Xinyan Pan8Chanjuan Su9Ziteng Li10Li Wang11Li Wang12Jiang Gu13Jiang Gu14Department of Pathology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, ChinaThe Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, ChinaProvincial 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, ChinaDepartment of Gynecology, Peking University Cancer Hospital Yunnan, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Pathology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, ChinaThe Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, ChinaProvincial 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, ChinaDepartment of Pathology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, ChinaThe Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, ChinaProvincial 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, ChinaProvincial 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, ChinaDepartment of Pathology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, ChinaThe Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, ChinaProvincial 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, ChinaJinxin Research Institute for Reproductive Medicine and Genetics, Xinan Hospital for Maternal and Child Health Care, Chengdu, ChinaBackgroundOur 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.ObjectTo elucidate the distribution of IgG4, Treg cells, and M2 macrophages in TLS and to assess the impact of IgG4 on macrophage polarization.MethodsEsophageal 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.ResultsIgG4 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.ConclusionIgG4 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1497783/fullimmunoglobulin G4tertiary lymphoid structuretumor microenvironmentmacrophage polarizationinterleukin-10 |
| spellingShingle | Hui Wang Hui Wang Jirui Li Yinghai Wang Yang Chen Yang Chen Weifeng Zhang Xinyan Pan Xinyan Pan Chanjuan Su Ziteng Li Li Wang Li Wang Jiang Gu Jiang Gu IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression Frontiers in Immunology immunoglobulin G4 tertiary lymphoid structure tumor microenvironment macrophage polarization interleukin-10 |
| title | IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression |
| title_full | IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression |
| title_fullStr | IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression |
| title_full_unstemmed | IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression |
| title_short | IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression |
| title_sort | igg4 mediated m2 macrophage polarization in tertiary lymphoid structures of esophageal cancer implications for immunosuppression |
| topic | immunoglobulin G4 tertiary lymphoid structure tumor microenvironment macrophage polarization interleukin-10 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1497783/full |
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