Proteoglycan isolated from Phellinus linteus inhibits tumor growth through mechanisms leading to an activation of CD11c⁺CD8⁺ DC and type I helper T cell‐dominant immune state

Dendritic cells (DC) are known to not only induce the activation of T cells, but are also associated with the polarization of T cells. This study investigated whether or not proteoglycan (PG) isolated from Phellinus linteus induces the phenotypic and functional maturation of CD11c⁺ DC in vitro and in vivo. PG was found to induce the phenotypic and functional maturation of bone marrow‐derived DC via Toll‐like receptors (TLR) 2 and 4 in vitro. Administration of PG in vivo strongly inhibited the MCA‐102 tumor growth and increase in vivo. The ratio of CD8⁺ DC to CD8⁻ DC increased, and PG enhanced IL‐12 and IFN‐γ production, and expression of surface molecules including major histocompatibility complexes (MHC) classes I, MHC II, CD80, and CD86 in MCA‐102‐challenged mice. PG also caused a marked increase in the production of Th (helper T cells)‐1 cytokine (IFN‐γ) and a decrease in the production of Th‐2 cytokine (IL‐4) by splenic cells and inguinal lymph node cells in MCA‐102 tumor‐bearing mice. Furthermore, PG stimulated the proliferation of CD4⁺ and CD8⁺ T cells. In addition, a combination of PG and tumor lysate‐pulsed DC inhibited completely the growth of MCA‐102 cells in tumor‐bearing mice. These results indicate that the administration of PG inhibited the tumor growth through a mechanism leading to a Th‐1 dominant immune state and the activation of CD11c⁺CD8⁺ DC.