Therapeutic blockade of Foxp3 in experimental breast cancer models

GOTTARDO, MARÍA FLORENCIA; BAL DE KIER JOFFÉ, ELISA; SEILICOVICH, ADRIANA; MORENO AYALA, MARIELA A.; ASAD, ANTONELA SOFIA; JUAN JOSE LASARTE; IMSEN, MERCEDES; NOELIA CASARES; CANDOLFI, MARIANELA

BREAST CANCER RESEARCH AND TREATMENT

SPRINGER

Lugar: Berlin; Año: 2017 vol. 166 p. 393 - 405

0167-6806

PURPOSE:Regulatory T cells (Tregs) impair the clinical benefit of cancer immunotherapy. To optimize the antitumor efficacy of therapeutic dendritic cell (DC) vaccines, we aimed to inhibit Foxp3, a transcription factor required for Treg function.METHODS:Mice bearing established syngeneic LM3 and 4T1 breast tumors were treated with antitumor DC vaccines and a synthetic peptide (P60) that has been shown to inhibit Foxp3.RESULTS:Treatment with P60 improved the therapeutic efficacy of DC vaccines in these experimental models. In addition, monotherapy with P60 inhibited tumor growth in immunocompetent as well as in immuno-compromised animals bearing established tumors. We found expression of Foxp3 in human and murine breast tumor cells. P60 inhibited IL-10 secretion in breast cancer cells that expressed Foxp3.CONCLUSIONS:Our results suggest that Foxp3 blockade improves the therapeutic efficacy of DC vaccines by inhibition of Tregs and through a direct antitumor effect. This strategy could prove useful to neutralize the immunosuppressive microenvironment and to boost antitumor immunity in breast cancer.