Combining LY6E loaded DC therapy with pioglitazone improved the DC therapy effect for colorectal cancer treatment. LY6E pulsed DCs excites the CD8 positive immune responses against colorectal models. Pioglitazone inhibits IL-6 axis and formation of CRC cell lines proliferation through IL-6/STAT3 by influencing the immunosuppressive feature of the tumor microenvironment.