title: Metabolic inhibition of galectin-1-binding carbohydrates accentuates antitumor immunity.
abstract: Galectin-1 (Gal-1) has been shown to play a major role in tumor immune escape by inducing apoptosis of effector leukocytes and correlating with tumor aggressiveness and disease progression. Thus, targeting the Gal-1/Gal-1 ligand axis represents a promising cancer therapeutic approach. Here, to test the Gal-1-mediated tumor immune evasion hypothesis and demonstrate the importance of Gal-1-binding N-acetyllactosamines in controlling the fate and function of antitumor immune cells, we treated melanoma- or lymphoma-bearing mice with peracetylated 4-fluoro-glucosamine (4-F-GlcNAc), a metabolic inhibitor of N-acetyllactosamine biosynthesis, and analyzed tumor growth and immune profiles. We found that 4-F-GlcNAc spared Gal-1-mediated apoptosis of T cells and natural killer (NK) cells by decreasing their expression of Gal-1-binding determinants. 4-F-GlcNAc enhanced tumor lymphocytic infiltration and promoted elevations in tumor-specific cytotoxic T cells and IFN-γ levels, while lowering IL-10 production. Collectively, our data suggest that metabolic lowering of Gal-1-binding N-acetyllactosamines may attenuate tumor growth by boosting antitumor immune cell levels, representing a promising approach for cancer immunotherapy.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Filiberto
authors.initials: F
authors.lastname: Cedeno-Laurent
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Opperman
authors.forename: Steven R
authors.initials: SR
authors.lastname: Barthel
authors.forename: Danielle
authors.initials: D
authors.lastname: Hays
authors.forename: Tobias
authors.initials: T
authors.lastname: Schatton
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Xiaoying
authors.initials: X
authors.lastname: He
authors.forename: Khushi L
authors.initials: KL
authors.lastname: Matta
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Supko
authors.forename: Markus H
authors.initials: MH
authors.lastname: Frank
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dimitroff
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000606:Amino Sugars / Q000378:metabolism*; D000818:Animals; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D051917:Leukosialin / Q000502:physiology; D008223:Lymphoma / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000606:Amino Sugars; D037483:Galectin 1; D051917:Leukosialin; C497863:Spn protein, mouse; C089178:2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoroglucopyranose; D016753:Interleukin-10; C000458:N-acetyllactosamine; D007371:Interferon-gamma; D000117:Acetylglucosamine