Academic Journal
Sialylation in Colorectal Cancer Rewires Antitumor Immunity at the Peritoneal Metastatic Site.
| Title: | Sialylation in Colorectal Cancer Rewires Antitumor Immunity at the Peritoneal Metastatic Site. |
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| Authors: | van der Haar Àvila I; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Immunology and Infectious Diseases, Cancer Immunology, Amsterdam, the Netherlands., Lenos K; Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; Oncode Institute, Amsterdam, the Netherlands., Lorrain V; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Immunology and Infectious Diseases, Cancer Immunology, Amsterdam, the Netherlands., Nardini E; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Immunology and Infectious Diseases, Cancer Immunology, Amsterdam, the Netherlands., Rodríguez E; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Immunology and Infectious Diseases, Cancer Immunology, Amsterdam, the Netherlands., García-Vallejo JJ; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Immunology and Infectious Diseases, Cancer Immunology, Amsterdam, the Netherlands., van Kooyk Y; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Immunology and Infectious Diseases, Cancer Immunology, Amsterdam, the Netherlands., Grootjans J; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; Oncode Institute, Amsterdam, the Netherlands.; Department of Gastroenterology and Hepatology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands., van Vliet SJ; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Immunology and Infectious Diseases, Cancer Immunology, Amsterdam, the Netherlands. |
| Source: | European journal of immunology [Eur J Immunol] 2026 May; Vol. 56 (5), pp. e70204. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 1273201 Publication Model: Print Cited Medium: Internet ISSN: 1521-4141 (Electronic) Linking ISSN: 00142980 NLM ISO Abbreviation: Eur J Immunol Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2005->: Weinheim : Wiley-VCH Original Publication: Weinheim, Verlag Chemie GmbH. |
| MeSH Terms: | Colorectal Neoplasms*/immunology , Colorectal Neoplasms*/pathology , Colorectal Neoplasms*/metabolism , Peritoneal Neoplasms*/secondary , Peritoneal Neoplasms*/immunology , N-Acetylneuraminic Acid*/metabolism , N-Acetylneuraminic Acid*/immunology, Macrophages/immunology ; Dendritic Cells/immunology ; Liver Neoplasms/secondary ; Liver Neoplasms/immunology ; Neutrophils/immunology ; Polysaccharides/metabolism ; Polysaccharides/immunology ; Animals ; Mice ; Humans ; Cell Line, Tumor ; Female |
| Abstract: | Colorectal cancer (CRC) patients are frequently diagnosed with metastases to the peritoneal cavity. These patients have a dismal prognosis and only limited therapeutical benefits. Solid tumors, including CRC, often display elevated levels of sialylated glycan structures, acting as immune checkpoints for immune evasion. However, the detrimental effects of tumor sialylation on antitumor immunity at the peritoneal site remain unexplored. We uncovered that sialylation is higher in peritoneal metastases (PM) compared with primary CRC or liver metastases. Intraperitoneal injection of sialic acid-deficient CT26 CRC cells led to significantly less peritoneal tumor development and a lower peritoneal cancer index (PCI) score. Sialic acid-devoid tumors harbored higher numbers of live CD45+ cells, and the myeloid compartment of desialylated tumors showed increased levels of MHC-II+ macrophages and dendritic cells and significantly fewer neutrophils and CD206+ macrophages, correlating with a lower PCI score. In conclusion, the absence of sialylated glycans reprograms antitumor immunity and reduces tumor formation at the peritoneal site. (© 2026 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.) |
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| Grant Information: | 09150172210058 Netherlands ZONMW_ ZonMw; ImPACT Top Institute for Knowledge and Innovation; 12420,16816and13435/2021-1 Dutch Cancer Society (KWF) |
| Contributed Indexing: | Keywords: colorectal cancer; peritoneal metastasis; sialic acids; tumor immunity |
| Substance Nomenclature: | GZP2782OP0 (N-Acetylneuraminic Acid) 0 (Polysaccharides) |
| Entry Date(s): | Date Created: 20260519 Date Completed: 20260717 Latest Revision: 20260906 |
| Update Code: | 20260906 |
| PubMed Central ID: | PMC13185675 |
| DOI: | 10.1002/eji.70204 |
| PMID: | 42153609 |
| Database: | MEDLINE |
| ISSN: | 1521-4141 |
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| DOI: | 10.1002/eji.70204 |