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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.
Afiliação
  • Moreno Ayala MA; Instituto de Investigaciones Biomédicas (INBIOMED), Facultad de Medicina, CONICET, Universidad de Buenos Aires, Paraguay 2155, piso 10, Buenos Aires, C1121ABG, Argentina.
  • Gottardo MF; Instituto de Investigaciones Biomédicas (INBIOMED), Facultad de Medicina, CONICET, Universidad de Buenos Aires, Paraguay 2155, piso 10, Buenos Aires, C1121ABG, Argentina.
  • Imsen M; Departamento de Biología Celular e Histología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Asad AS; Instituto de Investigaciones Biomédicas (INBIOMED), Facultad de Medicina, CONICET, Universidad de Buenos Aires, Paraguay 2155, piso 10, Buenos Aires, C1121ABG, Argentina.
  • Bal de Kier Joffé E; Instituto de Investigaciones Biomédicas (INBIOMED), Facultad de Medicina, CONICET, Universidad de Buenos Aires, Paraguay 2155, piso 10, Buenos Aires, C1121ABG, Argentina.
  • Casares N; Departamento de Biología Celular e Histología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Lasarte JJ; Área Investigación, Instituto de Oncología Angel H. Roffo, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Seilicovich A; Program Immunology and Immunotherapy, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Avenida Pio XII 55, 31008, Pamplona, Spain.
  • Candolfi M; Instituto de Investigación Sanitaria de Navarra (IDISNA), Recinto de Complejo Hospitalario de Navarra, Irunlarrea 3, 31008, Pamplona, Spain.
Breast Cancer Res Treat ; 166(2): 393-405, 2017 Nov.
Article em En | MEDLINE | ID: mdl-28756536
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Neoplasias da Mama / Linfócitos T Reguladores / Fatores de Transcrição Forkhead / Peptídeos Penetradores de Células Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Breast Cancer Res Treat Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Argentina País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Neoplasias da Mama / Linfócitos T Reguladores / Fatores de Transcrição Forkhead / Peptídeos Penetradores de Células Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Breast Cancer Res Treat Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Argentina País de publicação: Holanda