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: Filiberto Cedeno-Laurent, Matthew J Opperman, Steven R Barthel, Danielle Hays, Tobias Schatton, Qian Zhan, Xiaoying He, Khushi L Matta, Jeffrey G Supko, Markus H Frank, George F Murphy, Charles J Dimitroff
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 132 Issue 2 Pg. 410-20 (Feb 2012) ISSN: 1523-1747 [Electronic] United States
• PMID: 22158550 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amino Sugars
• Galectin 1
• Leukosialin
• Spn protein, mouse
• 2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoroglucopyranose
• Interleukin-10
• N-acetyllactosamine
• Interferon-gamma
• Acetylglucosamine

Topics

• Acetylglucosamine (analogs & derivatives, pharmacology)
• Amino Sugars (metabolism)
• Animals
• Galectin 1 (antagonists & inhibitors, physiology)
• Interferon-gamma (immunology)
• Interleukin-10 (immunology)
• Leukosialin (physiology)
• Lymphoma (immunology)
• Melanoma, Experimental (immunology)
• Mice
• Mice, Inbred C57BL
• T-Lymphocytes, Cytotoxic (immunology)