iScience (Jul 2023)

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

Journal volume & issue
Vol. 26, no. 7
p. 106984

Abstract

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Summary: 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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