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however, its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple-negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumoral administration of Ad.P60 in breast-tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth, and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells and that gene-therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.<\/jats:p>","DOI":"10.3390\/v15091813","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T02:23:25Z","timestamp":1693189405000},"page":"1813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeting FOXP3 Tumor-Intrinsic Effects Using Adenoviral Vectors in Experimental Breast Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-560X","authenticated-orcid":false,"given":"Alejandro J.","family":"Nicola Candia","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas","family":"Garcia Fallit","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"},{"name":"Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3470-7824","authenticated-orcid":false,"given":"Jorge A.","family":"Pe\u00f1a Agudelo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"P\u00e9rez K\u00fcper","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazareno","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela A.","family":"Moreno Ayala","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"De Simone","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Fisiolog\u00eda Animal, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires C1428BFA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Giampaoli","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Fisiolog\u00eda Animal, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires C1428BFA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelia","family":"Casares","sequence":"additional","affiliation":[{"name":"Program Immunology and Immunotherapy, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA, CUN), 31008 Pamplona, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Seilicovich","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-3881","authenticated-orcid":false,"given":"Juan Jos\u00e9","family":"Lasarte","sequence":"additional","affiliation":[{"name":"Program Immunology and Immunotherapy, Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA, CUN), 31008 Pamplona, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4337-4163","authenticated-orcid":false,"given":"Flavia A.","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia y Tecnolog\u00eda \u201cDr. Cesar Milstein\u201d, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Saladillo C1440FFX, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianela","family":"Candolfi","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fimmu.2019.00043","article-title":"Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity","volume":"10","author":"Romano","year":"2019","journal-title":"Front. 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