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ST3Gal1 synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer

Garnham, Rebecca, Geh, Daniel, Nelson, Ryan, Ramon-Gill, Erik, Wilson, Laura, Schmidt, Edward N, Walker, Laura, Adamson, Beth, Buskin, Adriana, Hepburn, Anastasia, Hodgson, Kirsty, Kendall, Hannah, Frame, Fiona M, Maitland, Norman, Coffey, Kelly, Robson, Craig N, Elliott, David J, Heer, Rakesh, Macauley, Matthew, Munkley, Jennifer, Gaughan, Luke, Leslie, Jack and Scott, Emma (2023) ST3Gal1 synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer. bioRxiv.

Item Type: Article


Immune checkpoint blockade trials have yet to produce a robust anti-cancer response in prostate cancer patients as a monotherapy due to the immunosuppressed prostate cancer tumour immune microenvironment. ST3Gal1 and other sialyltransferases are implicated in cancer and immune suppression by synthesizing sialoglycans, which act as ligands for Siglec receptors. These checkpoints are important for the immune response. However, it’s unclear how the synthesis of Siglec ligands is regulated, and little is known about the role of sialoglycan-Siglec-axis in prostate cancer’s evasion of anti-tumour immunity. We report that ST3Gal1 levels negatively correlate with androgen signalling in prostate tumours. Utilising syngeneic mouse models, we demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion. Using mouse models, patient samples and in vitro models we show that ST3Gal1 synthesises sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. For the first time we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. Importantly, we show that 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.


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Depositing User: Rebecca Garnham


Item ID: 17653
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Catalogue record

Date Deposited: 03 Jul 2024 08:33
Last Modified: 03 Jul 2024 08:33


Author: Rebecca Garnham
Author: Daniel Geh
Author: Ryan Nelson
Author: Erik Ramon-Gill
Author: Laura Wilson
Author: Edward N Schmidt
Author: Laura Walker
Author: Beth Adamson
Author: Adriana Buskin
Author: Anastasia Hepburn
Author: Kirsty Hodgson
Author: Hannah Kendall
Author: Fiona M Frame
Author: Norman Maitland
Author: Kelly Coffey
Author: Craig N Robson
Author: David J Elliott
Author: Rakesh Heer
Author: Matthew Macauley
Author: Jennifer Munkley
Author: Luke Gaughan
Author: Jack Leslie
Author: Emma Scott

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine


Sciences > Biomedical Sciences
Sciences > Health Sciences

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