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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Main Authors: Jinyu Wang, Michela Manni, Anne Bärenwaldt, Ronja Wieboldt, Nicole Kirchhammer, Robert Ivanek, Michal Stanczak, Alfred Zippelius, David König, Natalia Rodrigues Manutano, Heinz Läubli
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-03-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
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.
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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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