Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity
Suppression of anticancer immune function is a key driver of tumorigenesis. Identifying molecular pathways that inhibit anticancer immunity is critical for developing novel immunotherapeutics. One such molecule that has recently been identified is the carbohydrate polysialic acid (polySia), whose ex...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1520948/full |
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| author | Olivia Drummond-Guy John Daly Angeline Wu Natalie Stewart Katy Milne Chloe Duff Brad H. Nelson Brad H. Nelson Brad H. Nelson Karla C. Williams Simon Wisnovsky |
| author_facet | Olivia Drummond-Guy John Daly Angeline Wu Natalie Stewart Katy Milne Chloe Duff Brad H. Nelson Brad H. Nelson Brad H. Nelson Karla C. Williams Simon Wisnovsky |
| author_sort | Olivia Drummond-Guy |
| collection | DOAJ |
| description | Suppression of anticancer immune function is a key driver of tumorigenesis. Identifying molecular pathways that inhibit anticancer immunity is critical for developing novel immunotherapeutics. One such molecule that has recently been identified is the carbohydrate polysialic acid (polySia), whose expression is dramatically upregulated on both cancer cells and immune cells in breast cancer patient tissues. The role of polySia in the anticancer immune response, however, remains incompletely understood. In this study, we profile polySia expression on both healthy primary immune cells and on infiltrating immune cells in the tumour microenvironment (TME). These studies reveal polySia expression on multiple immune cell subsets in patient breast tumors. We find that stimulation of primary T-cells and macrophages in vitro induces a significant upregulation of polySia expression. We subsequently show that polySia is appended to a range of different carrier proteins within these immune cells. Finally, we find that selective removal of polySia can significantly potentiate killing of breast cancer cells by innate immune cells. These studies implicate polySia as a significant negative regulator of anticancer immunity. |
| format | Article |
| id | doaj-art-ad7e74dc0c1d4525bea88b1803c70d07 |
| institution | OA Journals |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-ad7e74dc0c1d4525bea88b1803c70d072025-08-20T01:49:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-03-011510.3389/fonc.2025.15209481520948Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activityOlivia Drummond-Guy0John Daly1Angeline Wu2Natalie Stewart3Katy Milne4Chloe Duff5Brad H. Nelson6Brad H. Nelson7Brad H. Nelson8Karla C. Williams9Simon Wisnovsky10Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaDeeley Research Centre, British Columbia (BC) Cancer, Victoria, BC, CanadaDeeley Research Centre, British Columbia (BC) Cancer, Victoria, BC, CanadaDeeley Research Centre, British Columbia (BC) Cancer, Victoria, BC, CanadaDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaSuppression of anticancer immune function is a key driver of tumorigenesis. Identifying molecular pathways that inhibit anticancer immunity is critical for developing novel immunotherapeutics. One such molecule that has recently been identified is the carbohydrate polysialic acid (polySia), whose expression is dramatically upregulated on both cancer cells and immune cells in breast cancer patient tissues. The role of polySia in the anticancer immune response, however, remains incompletely understood. In this study, we profile polySia expression on both healthy primary immune cells and on infiltrating immune cells in the tumour microenvironment (TME). These studies reveal polySia expression on multiple immune cell subsets in patient breast tumors. We find that stimulation of primary T-cells and macrophages in vitro induces a significant upregulation of polySia expression. We subsequently show that polySia is appended to a range of different carrier proteins within these immune cells. Finally, we find that selective removal of polySia can significantly potentiate killing of breast cancer cells by innate immune cells. These studies implicate polySia as a significant negative regulator of anticancer immunity.https://www.frontiersin.org/articles/10.3389/fonc.2025.1520948/fullimmune cellscarbohydratesglycansmacrophagesT-cellsNK cells |
| spellingShingle | Olivia Drummond-Guy John Daly Angeline Wu Natalie Stewart Katy Milne Chloe Duff Brad H. Nelson Brad H. Nelson Brad H. Nelson Karla C. Williams Simon Wisnovsky Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity Frontiers in Oncology immune cells carbohydrates glycans macrophages T-cells NK cells |
| title | Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity |
| title_full | Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity |
| title_fullStr | Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity |
| title_full_unstemmed | Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity |
| title_short | Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity |
| title_sort | polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity |
| topic | immune cells carbohydrates glycans macrophages T-cells NK cells |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1520948/full |
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