Oral administration of xanthan gum enhances antitumor activity through Toll-like receptor 4

Purpose: Xanthan gum (XG) is a complex exopolysaccharide produced by the plant-pathogenic bacterium Xanthomonas campestris pv. and is widely used as a thickener or viscosifier. We examined in this study the antitumor effects of XG. Experimental design: Cytokine production by XG-stimulated murine macrophage cell lines, J772 and RAW264.7, and peritoneal adherent cells from wild type C57BL/6 mice, TLR2 or MyD88-deficient mice, C3H/HeN, and TLR4-mutant C3H/HeJ mice were examined. In order to examine in vivo antitumor effects of XG, mice were inoculated subcutaneously with tumor cells and administered orally with XG once every 5 days from 1 day before the tumor inoculation. Tumor growth, mouse survival, NK activity, and tumor-specific cytotoxicity were examined. Results: In vitro culture with XG induced interleukin-12 and tumor necrosis factor-alpha production from macrophages. XG stimulated macrophages in a MyD88-dependent manner and was mainly recognized by Toll-like receptor 4 (TLR4). Oral administration of XG significantly retarded tumor growth and prolonged survival of the mice inoculated subcutaneously with B16K^b melanoma cells. NK activity as well as tumor-specific cytotoxicity of CD8 T cells was augmented in the XG-treated mice. The in vivo antitumor effects of XG were also dependent on TLR-4, as C3H/HeJ mice, which lack TLR4 signaling, exhibited no effect of XG on the growth of syngeneic bladder tumor, MBT-2. Conclusion: These results suggest beneficial effects of oral administration of XG on immune-surveillance against neoplasms.