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

Rudjord-Levann, Asha M. ; Ye, Zilu ; Hafkenscheid, Lise ; Horn, Sabrina ; Wiegertjes, Renske ; Nielsen, Mathias A.I. ; Song, Ming ; Mathiesen, Caroline B.K. ; Stoop, Jesse and Stowell, Sean , et al. (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.

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organization
publishing date
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}},
}