Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages
Tumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) const...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2010/547179 |
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| author | P. Allavena M. Chieppa G. Bianchi G. Solinas M. Fabbri G. Laskarin A. Mantovani |
| author_facet | P. Allavena M. Chieppa G. Bianchi G. Solinas M. Fabbri G. Laskarin A. Mantovani |
| author_sort | P. Allavena |
| collection | DOAJ |
| description | Tumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate-binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM-associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin-1, MDL-1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG-72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti-MR antibody modulated cytokine production by TAM toward an immune-suppressive profile: increase of IL-10, absence of IL-12, and decrease of the Th1-attracting chemokine CCL3. This study highlights that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype. |
| format | Article |
| id | doaj-art-9c2ce0228daa4c0e84725d6dd10a8b59 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-9c2ce0228daa4c0e84725d6dd10a8b592025-02-03T01:27:51ZengWileyClinical and Developmental Immunology1740-25221740-25302010-01-01201010.1155/2010/547179547179Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated MacrophagesP. Allavena0M. Chieppa1G. Bianchi2G. Solinas3M. Fabbri4G. Laskarin5A. Mantovani6Deptartment Immunology & Inflammation, IRCCS Clinical Institute Humanitas, Rozzano, 20089 Milan, ItalyDepartment of Translational Medicine, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, ItalyEnvironmental Health Sciences Department, Mario Negri Institute, 20157 Milano, ItalyDeptartment Immunology & Inflammation, IRCCS Clinical Institute Humanitas, Rozzano, 20089 Milan, ItalyEuropean Commission, Joint Research Centre Institute for Health and Consumer Protection Molecular Biology and Genomics, 21020 (VA) Ispra, ItalyDepartment of Physiology and Immunology, University of Rijeka, 51000 Rijeka, CroatiaDeptartment Immunology & Inflammation, IRCCS Clinical Institute Humanitas, Rozzano, 20089 Milan, ItalyTumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate-binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM-associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin-1, MDL-1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG-72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti-MR antibody modulated cytokine production by TAM toward an immune-suppressive profile: increase of IL-10, absence of IL-12, and decrease of the Th1-attracting chemokine CCL3. This study highlights that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype.http://dx.doi.org/10.1155/2010/547179 |
| spellingShingle | P. Allavena M. Chieppa G. Bianchi G. Solinas M. Fabbri G. Laskarin A. Mantovani Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages Clinical and Developmental Immunology |
| title | Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages |
| title_full | Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages |
| title_fullStr | Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages |
| title_full_unstemmed | Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages |
| title_short | Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages |
| title_sort | engagement of the mannose receptor by tumoral mucins activates an immune suppressive phenotype in human tumor associated macrophages |
| url | http://dx.doi.org/10.1155/2010/547179 |
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