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Record W4392514676 · 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

2024· article· en· W4392514676 on OpenAlexafffund
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 J. Maitland, Kelly Coffey, Douglas W. Strand, Craig Robson, David J. Elliott, Rakesh Heer, Matthew S. Macauley, Jennifer Munkley, Luke Gaughan, Jack Leslie, Emma Scott

Bibliographic record

VenueCommunications Biology · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsUniversity of Alberta
FundersCanadian Glycomics NetworkNational Institute of Diabetes and Digestive and Kidney DiseasesBiotechnology and Biological Sciences Research CouncilMedical Research CouncilNatural Sciences and Engineering Research Council of CanadaCancer Research UKAcademy of Medical SciencesNewcastle UniversityMark Foundation For Cancer ResearchProstate Cancer UKMovember FoundationProstate Cancer FoundationAlberta InnovatesJGW Patterson FoundationDirectorate for Biological Sciences
KeywordsProstate cancerEnzalutamideImmune systemCancer researchImmune checkpointProstateCancerBlockadeImmunologyAndrogen receptorBiologyImmunotherapyReceptorMedicineInternal medicine

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.151
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.302
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations34
Published2024
Admission routes2
Has abstractyes

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