Tumor associated macrophages and tumor infiltrating regulatory T cells greatly hamper host-protective antitumor responses. Therefore, we utilized a novel immunomodulator, heat-killed (), to repolarize TAM and an agonistic GITR antibody (DTA-1) to reduce intratumoral regulatory T cell frequency for generation of a host-protective antitumor response. Although, the combination of and DTA-1was found to be effective against advanced stage tumors, however, or DTA-1 failed to do so when administered individually. The presence of high level of regulatory T cells abrogated the only induced antitumor functions, whereas only DTA-1 treatment was found to be ineffective due to its inability to induce TAM repolarization The combination therapy was found to be effective since DTA-1 treatment reduced the frequency of regulatory T cells to such an extent where they could not attenuate induced TAM repolarization Therefore, the combination therapy involving and DTA-1 may be utilized to the success of advanced stage solid tumor immunotherapies.