Immunologic targeting of FOXP3 in inflammatory breast cancer cells.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nair, S; Aldrich, AJ; McDonnell, E; Cheng, Q; Aggarwal, A; Patel, P; Williams, MM; Boczkowski, D; Lyerly, HK; Morse, MA; Devi, GR

Published Date

  • 2013

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • e53150 -

PubMed ID

  • 23341929

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0053150

Language

  • eng

Conference Location

  • United States