Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1

Asha M. Rudjord-Levann; Zilu Ye; Lise Hafkenscheid; Sabrina Horn; Renske Wiegertjes; Mathias A.I. Nielsen; Ming Song; Caroline B.K. Mathiesen; Jesse Stoop; Sean Stowell; Per Thor Straten; Hakon Leffler; Sergey Y. Vakhrushev; Sally Dabelsteen; Jesper V. Olsen; Hans H. Wandall

doi:10.1016/j.isci.2023.106984

Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1

Asha M. Rudjord-Levann, Zilu Ye, Lise Hafkenscheid, Sabrina Horn, Renske Wiegertjes, Mathias A.I. Nielsen, Ming Song, Caroline B.K. Mathiesen, Jesse Stoop, Sean Stowell, Per Thor Straten, Hakon Leffler, Sergey Y. Vakhrushev, Sally Dabelsteen, Jesper V. Olsen, Hans H. Wandall^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

12 Citationer (Scopus)

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Abstract

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.

Originalsprog	Engelsk
Artikelnummer	106984
Tidsskrift	iScience
Vol/bind	26
Udgave nummer	7
Antal sider	21
ISSN	2589-0042
DOI	https://doi.org/10.1016/j.isci.2023.106984
Status	Udgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by the European Commission (GlycoSkin H2020-ERC ), European Commission (Imgene H2020 ), Lundbeck Foundation , The Danish Research Councils (Sapere Aude Research Leader grant to HW), Danish National Research Foundation ( DNRF107 ), The Friis Foundation , The Michelsen Foundation , A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til Almene Formaal, Danish Strategic Research Council , Novo Nordisk Foundation ( NNF14CC0001 and NNF17SA0027704 ), and the program of excellence from the University of Copenhagen ( CDO2016 ). HL was supported by a research grant from Galecto Biotech . We are also grateful for excellent technical assistance from Karin Uch Hansen. We acknowledge the Flow Cytometry & Single Cell Core Facility and the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen.

Publisher Copyright:
© 2023 The Authors

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10.1016/j.isci.2023.106984Licens: CC BY-NC-ND

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Citationsformater

Rudjord-Levann, A. M., Ye, Z., Hafkenscheid, L., Horn, S., Wiegertjes, R., Nielsen, M. A. I., Song, M., Mathiesen, C. B. K., Stoop, J., Stowell, S., Straten, P. T., Leffler, H., Vakhrushev, S. Y., Dabelsteen, S., Olsen, J. V., & Wandall, H. H. (2023). Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1. iScience, 26(7), Artikel 106984. https://doi.org/10.1016/j.isci.2023.106984

Rudjord-Levann, AM, Ye, Z, Hafkenscheid, L, Horn, S, Wiegertjes, R, Nielsen, MAI, Song, M, Mathiesen, CBK, Stoop, J, Stowell, S, Straten, PT, Leffler, H, Vakhrushev, SY , Dabelsteen, S , Olsen, JV & Wandall, HH 2023, 'Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1', iScience, bind 26, nr. 7, 106984. https://doi.org/10.1016/j.isci.2023.106984

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abstract = "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.",

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AU - Rudjord-Levann, Asha M.

AU - Ye, Zilu

AU - Hafkenscheid, Lise

AU - Horn, Sabrina

AU - Wiegertjes, Renske

AU - Nielsen, Mathias A.I.

AU - Song, Ming

AU - Mathiesen, Caroline B.K.

AU - Stoop, Jesse

AU - Stowell, Sean

AU - Straten, Per Thor

AU - Leffler, Hakon

AU - Vakhrushev, Sergey Y.

AU - Dabelsteen, Sally

AU - Olsen, Jesper V.

AU - Wandall, Hans H.

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N2 - 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.

AB - 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.

KW - Cancer

KW - Immunology

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DO - 10.1016/j.isci.2023.106984

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