Siglec Signaling in the Tumor Microenvironment
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors that recognize sialoglycans – sialic acid containing glycans that are abundantly present on cell membranes. Siglecs are expressed on most immune cells and can modulate their activity and function. The majority of Sig...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.790317/full |
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| author | Eline J. H. van Houtum Christian Büll Christian Büll Lenneke A. M. Cornelissen Gosse J. Adema |
| author_facet | Eline J. H. van Houtum Christian Büll Christian Büll Lenneke A. M. Cornelissen Gosse J. Adema |
| author_sort | Eline J. H. van Houtum |
| collection | DOAJ |
| description | Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors that recognize sialoglycans – sialic acid containing glycans that are abundantly present on cell membranes. Siglecs are expressed on most immune cells and can modulate their activity and function. The majority of Siglecs contains immune inhibitory motifs comparable to the immune checkpoint receptor PD-1. In the tumor microenvironment (TME), signaling through the Siglec-sialoglycan axis appears to be enhanced through multiple mechanisms favoring tumor immune evasion similar to the PD-1/PD-L1 signaling pathway. Siglec expression on tumor-infiltrating immune cells appears increased in the immune suppressive microenvironment. At the same time, enhanced Siglec ligand expression has been reported for several tumor types as a result of aberrant glycosylation, glycan modifications, and the increased expression of sialoglycans on proteins and lipids. Siglec signaling has been identified as important regulator of anti-tumor immunity in the TME, but the key factors contributing to Siglec activation by tumor-associated sialoglycans are diverse and poorly defined. Among others, Siglec activation and signaling are co-determined by their expression levels, cell surface distribution, and their binding preferences for cis- and trans-ligands in the TME. Siglec binding preference are co-determined by the nature of the proteins/lipids to which the sialoglycans are attached and the multivalency of the interaction. Here, we review the current understanding and emerging conditions and factors involved in Siglec signaling in the TME and identify current knowledge gaps that exist in the field. |
| first_indexed | 2024-12-15T00:35:37Z |
| format | Article |
| id | doaj.art-0fc23e2420a546629d0454deae6bc930 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-15T00:35:37Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0fc23e2420a546629d0454deae6bc9302022-12-21T22:41:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.790317790317Siglec Signaling in the Tumor MicroenvironmentEline J. H. van Houtum0Christian Büll1Christian Büll2Lenneke A. M. Cornelissen3Gosse J. Adema4Radiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, NetherlandsCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkRadiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsRadiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsSialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors that recognize sialoglycans – sialic acid containing glycans that are abundantly present on cell membranes. Siglecs are expressed on most immune cells and can modulate their activity and function. The majority of Siglecs contains immune inhibitory motifs comparable to the immune checkpoint receptor PD-1. In the tumor microenvironment (TME), signaling through the Siglec-sialoglycan axis appears to be enhanced through multiple mechanisms favoring tumor immune evasion similar to the PD-1/PD-L1 signaling pathway. Siglec expression on tumor-infiltrating immune cells appears increased in the immune suppressive microenvironment. At the same time, enhanced Siglec ligand expression has been reported for several tumor types as a result of aberrant glycosylation, glycan modifications, and the increased expression of sialoglycans on proteins and lipids. Siglec signaling has been identified as important regulator of anti-tumor immunity in the TME, but the key factors contributing to Siglec activation by tumor-associated sialoglycans are diverse and poorly defined. Among others, Siglec activation and signaling are co-determined by their expression levels, cell surface distribution, and their binding preferences for cis- and trans-ligands in the TME. Siglec binding preference are co-determined by the nature of the proteins/lipids to which the sialoglycans are attached and the multivalency of the interaction. Here, we review the current understanding and emerging conditions and factors involved in Siglec signaling in the TME and identify current knowledge gaps that exist in the field.https://www.frontiersin.org/articles/10.3389/fimmu.2021.790317/fullSiglecssialic acidssialoglycanstumor microenvironmentimmune checkpointcancer |
| spellingShingle | Eline J. H. van Houtum Christian Büll Christian Büll Lenneke A. M. Cornelissen Gosse J. Adema Siglec Signaling in the Tumor Microenvironment Frontiers in Immunology Siglecs sialic acids sialoglycans tumor microenvironment immune checkpoint cancer |
| title | Siglec Signaling in the Tumor Microenvironment |
| title_full | Siglec Signaling in the Tumor Microenvironment |
| title_fullStr | Siglec Signaling in the Tumor Microenvironment |
| title_full_unstemmed | Siglec Signaling in the Tumor Microenvironment |
| title_short | Siglec Signaling in the Tumor Microenvironment |
| title_sort | siglec signaling in the tumor microenvironment |
| topic | Siglecs sialic acids sialoglycans tumor microenvironment immune checkpoint cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.790317/full |
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