Nature communications, 2021-02, Vol.12 (1), p.1270-1270, Article 1270
2021
Details
- Autor(en) / Beteiligte
- Titel
- Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9
- Ist Teil von
- Nature communications, 2021-02, Vol.12 (1), p.1270-1270, Article 1270
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Changes in glycosylation during tumour progression are a key hallmark of cancer. One of the glycan moieties generally overexpressed in cancer are sialic acids, which can induce immunomodulatory properties via binding to Siglec receptors. We here show that Pancreatic Ductal Adenocarcinoma (PDAC) tumour cells present an increased sialylation that can be recognized by Siglec-7 and Siglec-9 on myeloid cells. We identified the expression of the α2,3 sialyltransferases ST3GAL1 and ST3GAL4 as main contributor to the synthesis of ligands for Siglec-7 and Siglec-9 in tumour cells. Analysing the myeloid composition in PDAC, using single cell and bulk transcriptomics data, we identified monocyte-derived macrophages as contributors to the poor clinical outcome. Tumour-derived sialic acids dictate monocyte to macrophage differentiation via signalling through Siglec-7 and Siglec-9. Moreover, triggering of Siglec-9 in macrophages reduce inflammatory programmes, while increasing PD-L1 and IL-10 expression, illustrating that sialic acids modulate different myeloid cells. This work highlights a critical role for sialylated glycans in controlling immune suppression and provides new potential targets for cancer immunotherapy in PDAC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-21550-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_64cd1d7410f74f27b60dd9aca97082ae
- Format
- –
- Schlagworte
- Acids, Adenocarcinoma, Antigens, CD - genetics, Antigens, CD - metabolism, Antigens, Differentiation, Myelomonocytic - genetics, Antigens, Differentiation, Myelomonocytic - metabolism, Cancer, Cancer immunotherapy, Cell differentiation, Cell Differentiation - drug effects, Cell Line, Tumor, Clustered Regularly Interspaced Short Palindromic Repeats - genetics, Differentiation, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Glycan, Glycosylation, Humans, Immunomodulation, Immunotherapy, Inflammation, Interleukin 10, Lectins - genetics, Lectins - metabolism, Macrophages, Macrophages - cytology, Macrophages - drug effects, Macrophages - metabolism, Monocytes, Monocytes - cytology, Monocytes - drug effects, Monocytes - metabolism, Myeloid cells, Pancreas - metabolism, Pancreatic cancer, Pancreatic Neoplasms, Pancreatic Neoplasms - metabolism, PD-L1 protein, Phosphorylation - drug effects, Polysaccharides, Receptor mechanisms, Receptors, Sialic Acid Binding Immunoglobulin-like Lectins - genetics, Sialic Acid Binding Immunoglobulin-like Lectins - metabolism, Sialic acids, Sialic Acids - pharmacology, Tumors