<i>Rehmannia glutinosa</i>polysaccharide induces toll-like receptor 4 dependent spleen dendritic cell maturation and anti-cancer immunity

Abstract

<i>Rehmannia glutinosa</i> polysaccharide (RGP) has shown an activation of immune cells <i>in vitro</i>. However, the immune stimulatory effect of RGP in a mouse <i>in vivo</i> is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity <i>in vivo</i>. Treatments of RGP in C56BL/6 mice induced increased levels of co-stimulatory molecule expression and pro-inflammatory cytokine production in spleen DCs dependent on toll-like receptor 4 (TLR4), and those DCs promoted interferon-gamma (IFNγ) production in CD4⁺ and CD8⁺ T cells. RGP also enhanced ovalbumin (OVA) antigen (Ag)-specific immune activation in tumor-bearing mice, including Ag presentation in DCs, OT-I and OT-II T-cell proliferation, migration of OT-I and OT-II T cells into the B16-OVA tumor, OVA-specific IFNγ production, and the specific killing of OVA-coated splenocytes, which consequently inhibited B16-OVA tumor growth dependent on TLR4 and CD8⁺ T cells. Finally, the combination of RGP and self-Ag treatment efficiently inhibited CT26 carcinoma and B16 melanoma tumor growth in BLAB/c and C57BL/6 mice, respectively. These data demonstrate that RGP could be a useful adjuvant molecule for immunotherapy against cancer.