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

被引：15

作者：

Rudjord-Levann, Asha M. ^{[1
]}

Ye, Zilu ^{[1
,2
]}

Hafkenscheid, Lise ^{[1
]}

Horn, Sabrina ^{[1
]}

Wiegertjes, Renske ^{[1
]}

Nielsen, Mathias A. I. ^{[1
]}

Song, Ming ^{[1
]}

Mathiesen, Caroline B. K. ^{[1
]}

Stoop, Jesse ^{[1
]}

Stowell, Sean ^{[3
]}

Straten, Per Thor ^{[4
]}

Leffler, Hakon ^{[5
]}

Vakhrushev, Sergey Y. ^{[1
]}

Dabelsteen, Sally ^{[6
]}

Olsen, Jesper V. ^{[2
]}

Wandall, Hans H. ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Ctr Glycom, Dept Cellular & Mol Med, Copenhagen, Denmark

[2] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Copenhagen, Denmark

[3] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[4] Copenhagen Univ Hosp, Ctr Canc Immune Therapy, Herlev, Denmark

[5] Div Microbiol Immunol & Glycobiol, BMC C1228b,Klinikgatan 28, Lund, Sweden

[6] Univ Copenhagen, Sch Dent, Dept Oral Med & Pathol, Copenhagen, Denmark

来源：

ISCIENCE | 2023年 / 26卷 / 07期

基金：

欧盟地平线“2020”; 新加坡国家研究基金会;

关键词：

INTERFERON-GAMMA; GENE-EXPRESSION; IFN-GAMMA; FAMILY; CANCER; CELLS; MODULATORS; PHYSIOLOGY; MECHANISM; IMMUNITY;

D O I：

10.1016/j.isci.2023.106984

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：21

共 58 条

[1] The Plasma [Kynurenine]/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal [J].