Tumor associated macrophages and tumor infiltrating regulatory T cells greatly hamper host-protective antitumor responses. Therefore, we utilized a novel immunomodulator, heat-killed Mycobacterium indicus pranii (Mw), 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 Mw and DTA-1was found to be effective against advanced stage tumors, however, Mw or DTA-1 failed to do so when administered individually. The presence of high level of regulatory T cells abrogated the only Mw induced antitumor functions, whereas only DTA-1 treatment was found to be ineffective due to its inability to induce TAM repolarization in vivo. 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 Mw induced TAM repolarization in vivo. Therefore, the combination therapy involving Mw and DTA-1 may be utilized to the success of advanced stage solid tumor immunotherapies.
BT - Oncoimmunology C1 -http://www.ncbi.nlm.nih.gov/pubmed/25949923?dopt=Abstract
DO - 10.1080/2162402X.2014.995559 IS - 3 J2 - Oncoimmunology LA - eng N2 -Tumor associated macrophages and tumor infiltrating regulatory T cells greatly hamper host-protective antitumor responses. Therefore, we utilized a novel immunomodulator, heat-killed Mycobacterium indicus pranii (Mw), 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 Mw and DTA-1was found to be effective against advanced stage tumors, however, Mw or DTA-1 failed to do so when administered individually. The presence of high level of regulatory T cells abrogated the only Mw induced antitumor functions, whereas only DTA-1 treatment was found to be ineffective due to its inability to induce TAM repolarization in vivo. 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 Mw induced TAM repolarization in vivo. Therefore, the combination therapy involving Mw and DTA-1 may be utilized to the success of advanced stage solid tumor immunotherapies.
PY - 2015 EP - e995559 T2 - Oncoimmunology TI - The combination of a novel immunomodulator with a regulatory T cell suppressing antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor associated macrophages in situ. UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404885/pdf/koni-04-e995559.pdf VL - 4 SN - 2162-4011 ER -