Immunologic targeting of FOXP3 in inflammatory breast cancer cells

PLoS One. 2013;8(1):e53150. doi: 10.1371/journal.pone.0053150. Epub 2013 Jan 14.


The forkhead transcription factor FOXP3 is necessary for induction of regulatory T lymphocytes (Tregs) and their immunosuppressive function. We have previously demonstrated that targeting Tregs by vaccination of mice with murine FOXP3 mRNA-transfected dendritic cells (DCs) elicits FOXP3-specific T cell responses and enhances tumor immunity. It is clear that FOXP3 expression is not restricted to T-cell lineage and herein, using RT-PCR, flow cytometry, and western immunoblot we demonstrate for the first time that FOXP3 is expressed in inflammatory breast cancer (IBC) cells, SUM149 (triple negative, ErbB1-activated) and SUM190 (ErbB2-overexpressing). Importantly, FOXP3-specific T cells generated in vitro using human FOXP3 RNA-transfected DCs as stimulators efficiently lyse SUM149 cells. Interestingly, an isogenic model (rSUM149) derived from SUM149 with an enhanced anti-apoptotic phenotype was resistant to FOXP3-specific T cell mediated lysis. The MHC class I cellular processing mechanism was intact in both cell lines at the protein and transcription levels suggesting that the resistance to cytolysis by rSUM149 cells was not related to MHC class I expression or to the MHC class I antigen processing machinery in these cells. Our data suggest that FOXP3 may be an effective tumor target in IBC cells however increased anti-apoptotic signaling can lead to immune evasion.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Apoptosis / immunology
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Cytotoxicity, Immunologic
  • Female
  • Forkhead Transcription Factors / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Inflammatory Breast Neoplasms / immunology*
  • Inflammatory Breast Neoplasms / pathology*
  • Lymphocyte Activation / immunology
  • Mice
  • Phenotype
  • Recurrence
  • S-Phase Kinase-Associated Proteins / metabolism
  • Survival Analysis
  • T-Lymphocytes, Cytotoxic / immunology
  • X-Linked Inhibitor of Apoptosis Protein / metabolism


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Histocompatibility Antigens Class I
  • S-Phase Kinase-Associated Proteins
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Cyclin-Dependent Kinase Inhibitor p27

Grants and funding

This work was entirely supported by Department of Defense W81XWH-07-1-0392 (GRD) and in part by Department of Defense W81XWH-10-1-0339 (SN), Duke SROP training program (MMW) and Duke Graduate fellowship (EM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.