Therapeutic blockade of Foxp3 in experimental breast cancer models

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

BREAST CANCER RESEARCH AND TREATMENT

SPRINGER

Año: 2017 p. 1 - 13

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.