ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer.

Autor: Garnham R; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Geh D; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Nelson R; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Ramon-Gil E; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Wilson L; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Schmidt EN; Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada.; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Walker L; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Adamson B; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Buskin A; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Hepburn AC; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Hodgson K; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Kendall H; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Frame FM; Cancer Research Unit, Department of Biology, University of York, Heslington, North Yorkshire, YO10 5DD, UK., Maitland N; Cancer Research Unit, Department of Biology, University of York, Heslington, North Yorkshire, YO10 5DD, UK., Coffey K; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Strand DW; Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA., Robson CN; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Elliott DJ; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Heer R; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Macauley M; Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada.; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Munkley J; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Gaughan L; Newcastle University, Centre for Cancer, Newcastle University Translational and Clinical Research Institute, Newcastle, NE1 3BZ, UK., Leslie J; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK., Scott E; Newcastle University, Centre for Cancer, Newcastle University Biosciences Institute, Newcastle, NE1 3BZ, UK. emma.scott@newcastle.ac.uk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Mar 06; Vol. 7 (1), pp. 276. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1038/s42003-024-05924-0
Abstrakt: Immune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and prostate to promote immune suppression by synthesising sialoglycans, which act as ligands for Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in prostate tumours. We demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion through the synthesises of sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. Here, we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. These interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer.
(© 2024. The Author(s).)
Databáze: MEDLINE
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