Therapeutic blockade of Foxp3 in experimental breast cancer models
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...
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Published in | Breast cancer research and treatment Vol. 166; no. 2; pp. 393 - 405 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.11.2017
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0167-6806 1573-7217 |
DOI: | 10.1007/s10549-017-4414-2 |