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Breast Cancer Research and Treatment

, Volume 166, Issue 2, pp 393–405 | Cite as

Therapeutic blockade of Foxp3 in experimental breast cancer models

  • 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 CandolfiEmail author
Preclinical study

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.

Keywords

Regulatory T cells Dendritic cell vaccines Breast cancer Immunotherapy Foxp3 

Notes

Acknowledgements

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.

Supplementary material

10549_2017_4414_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Mariela A. Moreno Ayala
    • 1
  • María Florencia Gottardo
    • 1
    • 2
  • Mercedes Imsen
    • 1
  • Antonela S. Asad
    • 1
  • Elisa Bal de Kier Joffé
    • 2
    • 3
  • Noelia Casares
    • 4
    • 5
  • Juan José Lasarte
    • 4
    • 5
  • Adriana Seilicovich
    • 1
    • 2
  • Marianela Candolfi
    • 1
    Email author
  1. 1.Instituto de Investigaciones Biomédicas (INBIOMED), Facultad de MedicinaCONICET, Universidad de Buenos AiresBuenos AiresArgentina
  2. 2.Departamento de Biología Celular e Histología, Facultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina
  3. 3.Área Investigación, Instituto de Oncología Angel H. Roffo, Facultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina
  4. 4.Program Immunology and ImmunotherapyCentro de Investigación Médica Aplicada (CIMA), PamplonaPamplonaSpain
  5. 5.Instituto de Investigación Sanitaria de Navarra (IDISNA)Recinto de Complejo Hospitalario de NavarraPamplonaSpain

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