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29.07.2017 | Preclinical study

Therapeutic blockade of Foxp3 in experimental breast cancer models

verfasst von: Mariela A. Moreno Ayala, María Florencia Gottardo, Mercedes Imsen, Antonela S. Asad, Elisa Bal de Kier Joffé, Noelia Casares, Juan José Lasarte, Adriana Seilicovich, Marianela Candolfi

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2017

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Abstract

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.

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Titel: Therapeutic blockade of Foxp3 in experimental breast cancer models
verfasst von: Mariela A. Moreno Ayala
María Florencia Gottardo
Mercedes Imsen
Antonela S. Asad
Elisa Bal de Kier Joffé
Noelia Casares
Juan José Lasarte
Adriana Seilicovich
Marianela Candolfi
Publikationsdatum: 29.07.2017
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4414-2

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Springer Medizin

Therapeutic blockade of Foxp3 in experimental breast cancer models

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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