Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer
Interactions between sialylated glycans and sialic acid-binding immunoglobulin-like lectin (Siglec) receptors have been recently described as potential new immune checkpoint that can be targeted to improve anticancer immunity. Myeloid cells have been reported to express a wide range of different Sig...
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Frontiers Media S.A.
2022-03-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.828916/full |
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author | Jinyu Wang Michela Manni Anne Bärenwaldt Ronja Wieboldt Nicole Kirchhammer Robert Ivanek Robert Ivanek Michal Stanczak Alfred Zippelius Alfred Zippelius David König David König Natalia Rodrigues Manutano Heinz Läubli Heinz Läubli |
author_facet | Jinyu Wang Michela Manni Anne Bärenwaldt Ronja Wieboldt Nicole Kirchhammer Robert Ivanek Robert Ivanek Michal Stanczak Alfred Zippelius Alfred Zippelius David König David König Natalia Rodrigues Manutano Heinz Läubli Heinz Läubli |
author_sort | Jinyu Wang |
collection | DOAJ |
description | Interactions between sialylated glycans and sialic acid-binding immunoglobulin-like lectin (Siglec) receptors have been recently described as potential new immune checkpoint that can be targeted to improve anticancer immunity. Myeloid cells have been reported to express a wide range of different Siglecs; however, their expression and functions on cancer-associated dendritic cells (DCs) were not fully characterized. We found that classical conventional DCs (cDCs) from cancer patient samples have a high expression of several inhibitory Siglecs including Siglec-7, Siglec-9, and Siglec-10. In subcutaneous murine tumor models, we also found an upregulation of the inhibitory Siglec-E receptor on cancer-associated cDCs. DC lines and bone marrow-derived DCs (BMDCs) with expression of these inhibitory Siglecs showed impaired maturation states on transcriptome and protein level. Furthermore, ablation of these inhibitory Siglecs from DCs enhanced their capability to prime antigen-specific T cells and induce proliferation. Our work provides a deeper understanding of the influence of inhibitory Siglecs on DCs and reveals a potential new target to improve cancer immunotherapy. |
first_indexed | 2024-12-10T17:22:09Z |
format | Article |
id | doaj.art-01a0e7344b054a58811118acfbbed626 |
institution | Directory Open Access Journal |
issn | 2296-634X |
language | English |
last_indexed | 2024-12-10T17:22:09Z |
publishDate | 2022-03-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cell and Developmental Biology |
spelling | doaj.art-01a0e7344b054a58811118acfbbed6262022-12-22T01:39:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-03-011010.3389/fcell.2022.828916828916Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in CancerJinyu Wang0Michela Manni1Anne Bärenwaldt2Ronja Wieboldt3Nicole Kirchhammer4Robert Ivanek5Robert Ivanek6Michal Stanczak7Alfred Zippelius8Alfred Zippelius9David König10David König11Natalia Rodrigues Manutano12Heinz Läubli13Heinz Läubli14Department of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandSwiss Institute of Bioinformatics, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDivision of Oncology, Department of Theragnostic, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDivision of Oncology, Department of Theragnostic, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital and University of Basel, Basel, SwitzerlandDivision of Oncology, Department of Theragnostic, University Hospital Basel, Basel, SwitzerlandInteractions between sialylated glycans and sialic acid-binding immunoglobulin-like lectin (Siglec) receptors have been recently described as potential new immune checkpoint that can be targeted to improve anticancer immunity. Myeloid cells have been reported to express a wide range of different Siglecs; however, their expression and functions on cancer-associated dendritic cells (DCs) were not fully characterized. We found that classical conventional DCs (cDCs) from cancer patient samples have a high expression of several inhibitory Siglecs including Siglec-7, Siglec-9, and Siglec-10. In subcutaneous murine tumor models, we also found an upregulation of the inhibitory Siglec-E receptor on cancer-associated cDCs. DC lines and bone marrow-derived DCs (BMDCs) with expression of these inhibitory Siglecs showed impaired maturation states on transcriptome and protein level. Furthermore, ablation of these inhibitory Siglecs from DCs enhanced their capability to prime antigen-specific T cells and induce proliferation. Our work provides a deeper understanding of the influence of inhibitory Siglecs on DCs and reveals a potential new target to improve cancer immunotherapy.https://www.frontiersin.org/articles/10.3389/fcell.2022.828916/fullsialic acidtumor immunologyglyco-immune checkpointantigenantigen processing |
spellingShingle | Jinyu Wang Michela Manni Anne Bärenwaldt Ronja Wieboldt Nicole Kirchhammer Robert Ivanek Robert Ivanek Michal Stanczak Alfred Zippelius Alfred Zippelius David König David König Natalia Rodrigues Manutano Heinz Läubli Heinz Läubli Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer Frontiers in Cell and Developmental Biology sialic acid tumor immunology glyco-immune checkpoint antigen antigen processing |
title | Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer |
title_full | Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer |
title_fullStr | Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer |
title_full_unstemmed | Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer |
title_short | Siglec Receptors Modulate Dendritic Cell Activation and Antigen Presentation to T Cells in Cancer |
title_sort | siglec receptors modulate dendritic cell activation and antigen presentation to t cells in cancer |
topic | sialic acid tumor immunology glyco-immune checkpoint antigen antigen processing |
url | https://www.frontiersin.org/articles/10.3389/fcell.2022.828916/full |
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