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Lookup NU author(s): Rebecca Garnham, Dr Daniel Geh, Ryan Nelson, Erik Ramon Gil, Laura WilsonORCiD, Dr Laura Walker, Dr Beth Adamson, Adriana Buskin, Dr Anastasia Hepburn, Dr Kirsty Hodgson, Hannah Kendall, Dr Kelly Coffey, Professor Craig Robson, Professor David Elliott, Professor Rakesh Heer, Dr Jennifer Munkley, Dr Luke GaughanORCiD, Dr Jack LeslieORCiD, Dr Emma ScottORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.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.
Author(s): Garnham R, Geh D, Nelson R, Ramon-Gil E, Wilson L, Schmidt EN, Walker L, Adamson B, Buskin A, Hepburn AC, Hodgson K, Kendall H, Frame FM, Maitland N, Coffey K, Strand DW, Robson CN, Elliott DJ, Heer R, Macauley M, Munkley J, Gaughan L, Leslie J, Scott E
Publication type: Article
Publication status: Published
Journal: Communications Biology
Year: 2024
Volume: 7
Issue: 1
Online publication date: 06/03/2024
Acceptance date: 16/02/2024
Date deposited: 19/03/2024
ISSN (electronic): 2399-3642
Publisher: Nature Research
URL: https://doi.org/10.1038/s42003-024-05924-0
DOI: 10.1038/s42003-024-05924-0
Data Access Statement: All data presented in this study have been deposited to Figshare (https://doi.org/10.6084/m9.figshare.24794589). Source data for Figs. 1b, 2c and 3j are available in Supplementary Data. Uncropped and unedited western blots are available in Supplementary Fig. 6. Sources for all publicly available datasets analysed in this manuscript are available in Supplementary Table 4
PubMed id: 38448753
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