Anti-tumor activity of vitamin C through the maintenance of IFN-producing dendritic cell (IKDC) population. (40.20)

Abstract

Abstract Natural killer (NK) cells play an important role in elimination of altered self cell, such as tumor cells. Recently, vitamin C is an essential component for augmentation of NK cell activity, especially in cancer patients. In this study, the effects of vitamin C on the anti-tumor activity of NKDC (CD49b+CD11c+NK1.1+) were investigated in Gulo(-/-) mice, which can not biosynthesize vitamin C like human beings. Body weight and the size of spleen of vitamin C depleted Gulo(-/-) mice was significantly decreased at 2 weeks after vitamin C depletion, comparing to those of wild type or vitamin C-supplemented Gulo(-/-) mice. To investigate the function of NKDC, CD49b+cells from splenocytes were isolated by MACS and then analyzed by flow cytometry. As a result, the number of NKDC population was completely reduced in vitamin C depleted Gulo(-/-) mice, which showed decrease of a secretion of IFN-gamma ƒ×. In addition, Fms-like tyrosine kinase 3 ligand (Flt3L), which stimulates the expansion and differentiation of IKDCs, was significantly reduced in vitamin C depleted Gulo(-/-) mice serum. Finally, the anti-tumor function of splenocytes from vitamin C depleted Gulo(-/-) mice was decreased, compared with those of wild type or vitamin C supplemented Gulo(-/-) mice. Taken together, it suggests that vitamin C shows their anti-tumor activity through the maintenance of Flt3L and the number of IKDC population.