Analysis of the glyco-code in pancreatic ductal adenocarcinoma identifies glycan-mediated immune regulatory circuits

Ernesto Rodriguez, Kelly Boelaars, Kari Brown, Katarina Madunić, Thomas van Ee, Frederike Dijk, Joanne Verheij, R J Eveline Li, Sjoerd T T Schetters, Laura L Meijer, Tessa Y S Le Large, Else Driehuis, Hans Clevers, Sven C M Bruijns, Tom O'Toole, Sandra J van Vliet, Maarten F Bijlsma, Manfred Wuhrer, Geert Kazemier, Elisa GiovannettiJuan J Garcia-Vallejo, Yvette van Kooyk

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a 5-year survival rate of only 9%. Despite the fact that changes in glycosylation patterns during tumour progression have been reported, no systematic approach has been conducted to evaluate its potential for patient stratification. By analysing publicly available transcriptomic data of patient samples and cell lines, we identified here two specific glycan profiles in PDAC that correlated with progression, clinical outcome and epithelial to mesenchymal transition (EMT) status. These different glycan profiles, confirmed by glycomics, can be distinguished by the expression of O-glycan fucosylated structures, present only in epithelial cells and regulated by the expression of GALNT3. Moreover, these fucosylated glycans can serve as ligands for DC-SIGN positive tumour-associated macrophages, modulating their activation and inducing the production of IL-10. Our results show mechanisms by which the glyco-code contributes to the tolerogenic microenvironment in PDAC.

Original languageEnglish
Pages (from-to)41
JournalCommunications Biology
Volume5
Issue number1
DOIs
Publication statusPublished - 11 Jan 2022

Keywords

  • Carcinoma, Pancreatic Ductal/genetics
  • Epithelial-Mesenchymal Transition/genetics
  • Glycoproteins/chemistry
  • Glycosylation
  • Humans
  • Pancreas/metabolism
  • Pancreatic Neoplasms/genetics
  • Polysaccharides/chemistry

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