Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1
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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; Stowell, Sean; Straten, Per Thor; Leffler, Hakon; Vakhrushev, Sergey Y.; Dabelsteen, Sally; Olsen, Jesper V.; Wandall, Hans H.
In: iScience, Vol. 26, No. 7, 106984, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1
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.
N1 - Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
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
U2 - 10.1016/j.isci.2023.106984
DO - 10.1016/j.isci.2023.106984
M3 - Journal article
C2 - 37534161
AN - SCOPUS:85161718499
VL - 26
JO - iScience
JF - iScience
SN - 2589-0042
IS - 7
M1 - 106984
ER -
ID: 360682643