Limited impact of cancer-derived gangliosides on anti-tumor immunity in colorectal cancer
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- Irene van der Haar Àvila
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam , de Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands
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- Tao Zhang
- Center for Proteomics and Metabolomics, Leiden University Medical Center , Albinusdreef 2, 2333 ZA Leiden, the Netherlands
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- Victor Lorrain
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam , de Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands
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- Florance de Bruin
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam , de Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands
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- Tianne Spreij
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam , de Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands
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- Hitoshi Nakayama
- Graduate School of Health Care and Nursing , Laboratory of Biochemistry, , 2-5-1 Takasu Urayasu-shi, Chiba, 279-0023, Japan
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- Kazuhisa Iwabuchi
- Graduate School of Health Care and Nursing , Laboratory of Biochemistry, , 2-5-1 Takasu Urayasu-shi, Chiba, 279-0023, Japan
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- Juan J García-Vallejo
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam , de Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands
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- Manfred Wuhrer
- Center for Proteomics and Metabolomics, Leiden University Medical Center , Albinusdreef 2, 2333 ZA Leiden, the Netherlands
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- Yvette van Kooyk
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam , de Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands
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- Sandra J van Vliet
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam , de Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands
書誌事項
- 公開日
- 2024-05-24
- 資源種別
- journal article
- 権利情報
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- https://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.1093/glycob/cwae036
- 公開者
- Oxford University Press (OUP)
説明
<jats:title>Abstract</jats:title> <jats:p>Aberrant glycosylation is a key mechanism employed by cancer cells to evade immune surveillance, induce angiogenesis and metastasis, among other hallmarks of cancer. Sialic acids, distinctive terminal glycan structures located on glycoproteins or glycolipids, are prominently upregulated across various tumor types, including colorectal cancer (CRC). Sialylated glycans modulate anti-tumor immune responses through their interactions with Siglecs, a family of glycan-binding receptors with specificity for sialic acid-containing glycoconjugates, often resulting in immunosuppression. In this paper, we investigated the immunomodulatory function of ST3Gal5, a sialyltransferase that catalyzes the addition of α2-3 sialic acids to glycosphingolipids, since lower expression of ST3Gal5 is associated with better survival of CRC patients. We employed CRISPR/Cas9 to knock out the ST3Gal5 gene in two murine CRC cell lines MC38 and CT26. Glycomics analysis confirmed the removal of sialic acids on glycolipids, with no discernible impact on glycoprotein sialylation. Although knocking out ST3Gal5 in both cell lines did not affect in vivo tumor growth, we observed enhanced levels of regulatory T cells in CT26 tumors lacking ST3Gal5. Moreover, we demonstrate that the absence of ST3Gal5 affected size and blood vessel density only in MC38 tumors. In summary, we ascertain that sialylation of glycosphingolipids has a limited influence on the anti-tumor immune response in CRC, despite detecting alterations in the tumor microenvironment, possibly due to a shift in ganglioside abundance.</jats:p>
収録刊行物
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- Glycobiology
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Glycobiology 34 (7), 2024-05-24
Oxford University Press (OUP)
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360869855563067904
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- ISSN
- 14602423
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
