The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion
Open accessAbstract
The increase of cell surface sialic acid is a characteristic shared by many tumor types. A correlation between hypersialylation and immunoprotection has been observed, but few hypotheses have provided a mechanistic understanding of this immunosuppressive phenomenon. Here, we show that increasing sialylated glycans on cancer cells inhibits human NK cell activation through the recruitment of Siglec-7. Key to these findings was the use of glycopolymers end-functionalized with phospholipids, which enable the introduction of synthetically defined glycans onto cancer cell surfaces. Remodeling the sialylation status of cancer cells affected the susceptibility to NK cell cytotoxicity via Siglec-7 engagement in a variety of tumor types. These results support a model in which hypersialylation offers a selective advantage to tumor cells under pressure from NK immunosurveillance by increasing Siglec ligands. We also exploited this finding to protect allogeneic and xenogeneic primary cells from NK-mediated killing suggesting the potential of Siglecs as therapeutic targets in cell transplant therapy.
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Cites
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Cited by
Concepts of extracellular matrix remodelling in tumour progression and metastasis
Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J., & Werb, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-18794-x · Cited by 2,296
Siglec-mediated regulation of immune cell function in disease
Macauley, M. S., Crocker, P. R., & Paulson, J. C. (2014) · Nature Reviews Immunology · doi:10.1038/nri3737 · Cited by 1,122
Glycosylation: mechanisms, biological functions and clinical implications
He, M., Zhou, X., & Wang, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01886-1 · Cited by 499
Sialic acids sweeten a tumor's life
Büll, C., Stoel, M. A., den Brok, M. H., & Adema, G. J. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0728 · Cited by 496
Sialic acids in cancer biology and immunity
Pearce, O. M. T., & Läubli, H. (2016) · Glycobiology · doi:10.1093/glycob/cwv097 · Cited by 470
Metadata
- Authors
- Hudak, J. E., Canham, S. M., & Bertozzi, C. R.
- Venue
- Nature Chemical Biology
- Published
- 2013-11-24
- Volume
- 10
- Issue
- 1
- Pages
- 69-75
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2144577119
- Cited by
- 485
- References
- 53
- FWCI
- 9.28
- Type
- journal article
- Language
- en
- Open access
- green
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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