Garnham, Rebecca, Geh, Daniel, Nelson, Ryan, Ramon-Gil, Erik, Wilson, Laura, Schmidt, Edward N, Walker, Laura, Adamson, Beth, Buskin, Adriana, Hepburn, Anastasia C, Hodgson, Kirsty, Kendall, Hannah, Frame, Fiona M, Maitland, Norman, Coffey, Kelly, Strand, Douglas W, Robson, Craig N, Elliott, David J, Heer, Rakesh, Macauley, Matthew, Munkley, Jennifer, Gaughan, Luke, Leslie, Jack and Scott, Emma (2024) ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer. Communications Biology, 7. ISSN 2399-3642
Document
-
s42003-024-05924-0.pdf
Available under License Creative Commons Attribution.
Abstract
Abstract
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.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Depositing User: | Rebecca Garnham |
| URI: | https://sure.sunderland.ac.uk/id/eprint/17652 |
Further Details
More Information
Identifiers
Users with ORCIDS
Catalogue record
Contributors
University Divisions
Subjects
Actions (login required)
Dimensions
DimensionsDownload Statistics
Downloads per month over past year