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Cancer immunomodulation by carbohydrate ligands for the lymphocyte receptor NKR-P1
M Pospisil1, L Vannucci, O Horvath
1Department of Immunology and Gnotobiology, Laboratory of Natural Cell Immunity, Institute of Microbiology, Academy of Sciences, Prague 14220, Czech Republic.
Abstract:
Natural killer (NK) and T cells express a superfamily of proteins with structural features of C-type lectins. Recombinantly prepared soluble form of rat NKR-P1 (CD161) recognized carbohydrate GalNac and GlcNac moieties. Ganglioside GM2 and heparin related-IS oligosaccharides representing the high affinity ligands for this receptor, increased the sensitivity of targets for killing by the rat effectors isolated from blood and spleen in vitro. Based on these results, we investigated in vivo the possible therapeutic effect of GM2 and IS carried by liposomes during induced rat colorectal carcinogenesis. The reduction of cancer incidence versus the controls (50% vs 88.88%), approached the 5-fluorouracil treatment (41.66%).
Insights
Natural killer (NK) cells and T cells utilize C-type lectin proteins. Ganglioside GM2 and heparin-related oligosaccharides (IS) enhanced NK cell activity and reduced colorectal cancer incidence in rats.
Area of Science:
- Immunology
- Carbohydrate Chemistry
- Cancer Research
Background:
- Natural killer (NK) and T cells express C-type lectin-like proteins.
- The rat NKR-P1 (CD161) receptor binds to specific carbohydrate structures.
Purpose of the Study:
- To investigate the therapeutic potential of ganglioside GM2 and heparin-related oligosaccharides (IS) in a rat model of colorectal cancer.
- To assess the effect of GM2 and IS on cancer incidence when delivered via liposomes.
Main Methods:
- Recombinant soluble rat NKR-P1 was used to identify its carbohydrate ligands.
- In vitro studies assessed the effect of GM2 and IS on the cytotoxic activity of rat NK and T cells.
- Liposomal formulations of GM2 and IS were administered to rats during induced colorectal carcinogenesis.
Main Results:
- Rat NKR-P1 recognized GalNac and GlcNac moieties, with ganglioside GM2 and IS oligosaccharides identified as high-affinity ligands.
- GM2 and IS significantly increased the sensitivity of target cells for killing by rat effector cells in vitro.
- Liposomal GM2 and IS administration reduced colorectal cancer incidence in rats by 50%, comparable to 5-fluorouracil treatment (41.66% reduction).
Conclusions:
- Ganglioside GM2 and heparin-related IS oligosaccharides can enhance NK cell-mediated cytotoxicity.
- Liposomal delivery of GM2 and IS demonstrates significant therapeutic potential in reducing colorectal carcinogenesis in a rat model.