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

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

doi:10.1038/s42003-024-05924-0

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

Rebecca Garnham, Daniel Geh, Ryan Nelson, Erik Ramon-Gil, Laura Wilson, Edward N. Schmidt, Laura Walker, Beth Adamson, Adriana Buskin, Anastasia C. Hepburn, Kirsty Hodgson, Hannah Kendall, Fiona M. Frame, Norman Maitland, Kelly Coffey, Douglas W. Strand, Craig N. Robson, David J. Elliott, Rakesh Heer, Matthew MacauleyJennifer Munkley, Luke Gaughan, Jack Leslie, Emma Scott

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	276
Journal	Communications Biology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s42003-024-05924-0
State	Published - Dec 2024

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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Garnham, R., Geh, D., Nelson, R., Ramon-Gil, E., Wilson, L., Schmidt, E. N., Walker, L., Adamson, B., Buskin, A., Hepburn, A. C., Hodgson, K., Kendall, H., Frame, F. M., Maitland, N., Coffey, K., Strand, D. W., Robson, C. N., Elliott, D. J., Heer, R., ... Scott, E. (2024). ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer. Communications Biology, 7(1), Article 276. https://doi.org/10.1038/s42003-024-05924-0

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 2024, 'ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer', Communications Biology, vol. 7, no. 1, 276. https://doi.org/10.1038/s42003-024-05924-0

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

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.",

author = "Rebecca Garnham and Daniel Geh and Ryan Nelson and Erik Ramon-Gil and Laura Wilson and Schmidt, {Edward N.} and Laura Walker and Beth Adamson and Adriana Buskin and Hepburn, {Anastasia C.} and Kirsty Hodgson and Hannah Kendall and Frame, {Fiona M.} and Norman Maitland and Kelly Coffey and Strand, {Douglas W.} and Robson, {Craig N.} and Elliott, {David J.} and Rakesh Heer and Matthew Macauley and Jennifer Munkley and Luke Gaughan and Jack Leslie and Emma Scott",

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doi = "10.1038/s42003-024-05924-0",

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AU - Garnham, Rebecca

AU - Geh, Daniel

AU - Nelson, Ryan

AU - Ramon-Gil, Erik

AU - Wilson, Laura

AU - Schmidt, Edward N.

AU - Walker, Laura

AU - Adamson, Beth

AU - Buskin, Adriana

AU - Hepburn, Anastasia C.

AU - Hodgson, Kirsty

AU - Kendall, Hannah

AU - Frame, Fiona M.

AU - Maitland, Norman

AU - Coffey, Kelly

AU - Strand, Douglas W.

AU - Robson, Craig N.

AU - Elliott, David J.

AU - Heer, Rakesh

AU - Macauley, Matthew

AU - Munkley, Jennifer

AU - Gaughan, Luke

AU - Leslie, Jack

AU - Scott, Emma

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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

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