Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1
(2023) In iScience 26(7).- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cancer, Immunology
- in
- iScience
- volume
- 26
- issue
- 7
- article number
- 106984
- publisher
- Elsevier
- external identifiers
-
- pmid:37534161
- scopus:85161718499
- ISSN
- 2589-0042
- DOI
- 10.1016/j.isci.2023.106984
- language
- English
- LU publication?
- yes
- id
- f59d5081-c271-40c3-860f-ef8fcf5b2e99
- date added to LUP
- 2023-09-05 15:16:18
- date last changed
- 2024-04-20 03:50:36
@article{f59d5081-c271-40c3-860f-ef8fcf5b2e99, abstract = {{<p>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.</p>}}, author = {{Rudjord-Levann, Asha M. and Ye, Zilu and Hafkenscheid, Lise and Horn, Sabrina and Wiegertjes, Renske and Nielsen, Mathias A.I. and Song, Ming and Mathiesen, Caroline B.K. and Stoop, Jesse and Stowell, Sean and Straten, Per Thor and Leffler, Hakon and Vakhrushev, Sergey Y. and Dabelsteen, Sally and Olsen, Jesper V. and Wandall, Hans H.}}, issn = {{2589-0042}}, keywords = {{Cancer; Immunology}}, language = {{eng}}, number = {{7}}, publisher = {{Elsevier}}, series = {{iScience}}, title = {{Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1}}, url = {{http://dx.doi.org/10.1016/j.isci.2023.106984}}, doi = {{10.1016/j.isci.2023.106984}}, volume = {{26}}, year = {{2023}}, }