Therapeutic blockade of Foxp3 in experimental breast cancer models
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.
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.
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.
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.
KeywordsRegulatory T cells Dendritic cell vaccines Breast cancer Immunotherapy Foxp3
This work was supported by Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET-PIP114-201101-00353 to M.C.; PIP11220120100261 to A.S.); Doctoral Fellowship to M.A.M.A., M.F.G. and A.S.A.); ANPYCT (PICT-2012-0830; PICT-2013-0310, PICT-2015-3309 to M.C.; PICT 2014-0334 to A.S.); Fundación Bunge y Born (“Jorge Oster” fellowship to M.A.M.A) and LALCEC fellowship to M.A.M.A. and by grants from Ministerio de Educación y Ciencia de España (SAF2016-78568-R), Fundación Ramón Areces and Gobierno de Navarra.
Compliance with ethical standards
Conflict of interest
All the authors declare no conflict of interest.
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