Published: 2023
Total Pages: 0
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Changes in glycosylation are a universal characteristic of malignant transformation, and tumor-specific glycan structures (which we denominate as the tumor glyco-code) are strongly associated with cancer progression and immune-modulation. Because immune cells express a large variety of glycan-binding receptors (called lectins), they can sense and respond to changes in the glycan signature of their environment; which often leads to the induction of inhibitory immune processes in those cells (Chapter I). In this thesis, we focus in the study of the tumor glyco-code of pancreatic ductal adenocarcinoma (PDAC) that represents one of the most aggressive malignancies, with a 5-year survival rate of only 9%. By analyzing publicly available transcriptomic data of patient samples, we studied two specific glycosylation signatures that correlate with progression, clinical outcome, and the modulation of the immune system: Fucosylation (Chapter II) and Sialylation (Chapter IV). In Chapter II, we identified that the presence of fucose-containing structures in cancer cells are associated with differences in their epithelial-to-mesenchymal transition status, the clinical outcome of patients and previously published molecular subtypes of PDAC. Moreover, these fucosylated structures can serve as ligands for the receptor DC-SIGN, present in tumour-associated macrophages (TAMs), and modulate their activation by inducing the overexpression of the anti-inflammatory cytokine IL-10. On the other hand, one of the glycan moieties generally overexpressed in cancer are sialic acids, which can modulate the function of immune cells via interaction with Siglec receptors (Chapter III).