Immunologic targeting of FOXP3 in inflammatory breast cancer cells.
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.
Duke Scholars
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Related Subject Headings
- X-Linked Inhibitor of Apoptosis Protein
- T-Lymphocytes, Cytotoxic
- Survival Analysis
- S-Phase Kinase-Associated Proteins
- Recurrence
- Phenotype
- Mice
- Lymphocyte Activation
- Inflammatory Breast Neoplasms
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- X-Linked Inhibitor of Apoptosis Protein
- T-Lymphocytes, Cytotoxic
- Survival Analysis
- S-Phase Kinase-Associated Proteins
- Recurrence
- Phenotype
- Mice
- Lymphocyte Activation
- Inflammatory Breast Neoplasms
- Humans