4.5 Article

Therapeutic blockade of Foxp3 in experimental breast cancer models

Journal

BREAST CANCER RESEARCH AND TREATMENT
Volume 166, Issue 2, Pages 393-405

Publisher

SPRINGER
DOI: 10.1007/s10549-017-4414-2

Keywords

Regulatory T cells; Dendritic cell vaccines; Breast cancer; Immunotherapy; Foxp3

Categories

Funding

  1. Consejo Nacional de Investigaciones Cientificas y Tecnologicas [CONICET-PIP114-201101-00353, PIP11220120100261]
  2. ANPYCT [PICT-2012-0830, PICT-2013-0310, PICT-2015-3309, PICT 2014-0334]
  3. Fundacion Bunge y Born
  4. LALCEC fellowship
  5. Ministerio de Educacion y Ciencia de Espana [SAF2016-78568-R]
  6. Fundacion Ramon Areces
  7. Gobierno de Navarra

Ask authors/readers for more resources

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. 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. 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. 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available