Therapeutic blockade of Foxp3 in experimental breast cancer: immunestimulation and direct antitumor effects

NICOLA CANDIA AJ; ASAD AS; SEILICOVICH A; GOTTARDO MF; BAL DE KIER JOFFÉ E; CANDOLFI M; MORENO AYALA MA; ZUCCATO CF; ZANETTI FA

Chicago

Congreso; Annual Meeting of American Association for Cancer Research; 2018

Our previous results indicate that systemic administration of a cell penetrating peptide (P60) that inhibits Foxp3, a transcription factor required for Treg function, improves the efficacy of antitumor vaccines in experimental breast cancer. Although there is controversy over the role of Foxp3 in tumor cells, we found that P60 inhibits survival and release of IL-10 in Foxp3+ breast tumor cells. Here we aimed to evaluate the regulatory pathways that control Foxp3 expression in LM3 breast tumor cells and to develop gene therapy vectors encoding P60. We assessed the effect of recombinant TGF-β, mTOR inhibitor rapamycin and COX-2 inhibitor indomethacin, all of which modulate Foxp3 expression in Tregs. Stimulation of LM3 cells with TGF-β and rapamicyn upregulated Foxp3 expression (p