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Galectin-1 induces ...
Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1
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- Rudjord-Levann, Asha M. (author)
- University of Copenhagen
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- Ye, Zilu (author)
- University of Copenhagen
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- Hafkenscheid, Lise (author)
- University of Copenhagen
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- Horn, Sabrina (author)
- University of Copenhagen
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- Wiegertjes, Renske (author)
- University of Copenhagen
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- Nielsen, Mathias A.I. (author)
- University of Copenhagen
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- Song, Ming (author)
- University of Copenhagen
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- Mathiesen, Caroline B.K. (author)
- University of Copenhagen
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- Stoop, Jesse (author)
- University of Copenhagen
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- Stowell, Sean (author)
- Brigham and Women's Hospital / Harvard Medical School
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- Straten, Per Thor (author)
- Copenhagen University Hospital
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- Leffler, Hakon (author)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Vakhrushev, Sergey Y. (author)
- University of Copenhagen
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Dabelsteen, Sally (author)
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Olsen, Jesper V. (author)
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- Wandall, Hans H. (author)
- University of Copenhagen
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: iScience. - 2589-0042. ; 26:7
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Abstract
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- Galectins are a group of carbohydrate-binding proteins with a presumed immunomodulatory role and an elusive function on antigen-presenting cells. Here we analyzed the expression of galectin-1 and found upregulation of galectin-1 in the extracellular matrix across multiple tumors. Performing an in-depth and dynamic proteomic and phosphoproteomic analysis of human macrophages stimulated with galectin-1, we show that galectin-1 induces a tumor-associated macrophage phenotype with increased expression of key immune checkpoint protein programmed cell death 1 ligand 1 (PD-L1/CD274) and immunomodulator indoleamine 2,3-dioxygenase-1 (IDO1). Galectin-1 induced IDO1 and its active metabolite kynurenine in a dose-dependent manner through JAK/STAT signaling. In a 3D organotypic tissue model system equipped with genetically engineered tumorigenic epithelial cells, we analyzed the cellular source of galectin-1 in the extracellular matrix and found that galectin-1 is derived from epithelial and stromal cells. Our results highlight the potential of targeting galectin-1 in immunotherapeutic treatment of human cancers.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Cancer
- Immunology
Publication and Content Type
- art (subject category)
- ref (subject category)
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Rudjord-Levann, ...
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Ye, Zilu
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Hafkenscheid, Li ...
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Horn, Sabrina
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Wiegertjes, Rens ...
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Nielsen, Mathias ...
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Song, Ming
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Mathiesen, Carol ...
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Stoop, Jesse
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Stowell, Sean
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Straten, Per Tho ...
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Leffler, Hakon
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Vakhrushev, Serg ...
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Dabelsteen, Sall ...
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Olsen, Jesper V.
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Wandall, Hans H.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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iScience
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Lund University