Abstract 1109: The antimicrobial peptide LL37 activates plasmacytoid dendritic cells in breast cancer

Abstract

Abstract Plasmacytoid dendritic cells (pDC) are the main producers of type I IFNs in response to viral and self nucleic acids that trigger endosomal TLR7 and 9. They have been recently described in various solid tumors. In breast tumors, we demonstrated that tumor-associated (TA)pDC exhibit a partially mature phenotype, suggesting that endogenous activating signals are present in tumor microenvironment (TME). Importantly, type I IFN was shown to play a major role in tumor immunosurveillance and we observed a type I IFN signature in human breast tumors. Altogether these observations lead us to investigate whether, in the initiating phase of tumorigenesis, TApDC might be activated by endogenous TLR ligands released in the TME that may trigger their IFN-a production, as observed in auto-immune disorders in response to [self nucleic acids-antimicrobial peptide LL37] complexes. First, we demonstrated that hCAP18/LL37 is expressed by a subset of CD45+ cells within the breast TME. Importantly, [self nucleic acids-LL37] complexes purified from breast TME were able to trigger IFN-a production in healthy pDC in vitro demonstrating their functionality. Finally, using syngenic murine mammary tumor models preliminary data showed that tumor cell growth is accelerated in IFNARko mice and pDC-depleted mice compared to wild-type mice suggesting a role for type I IFN and pDC in controlling early tumor development. Thus, our work aimed at demonstrating that restoring pDCs' immunosurveillance function might represent an attractive therapeutic strategy for localized breast tumors. Support : Ligue contre le cancer, Fondation ARC (SFI20111203835) and INCA (2011-1-PL BIO-12-IC-1). Citation Format: Nelly Vey, Elena Blanc, Vanja Sisirak, Sandra Thys, Céline Le Beux, Nadège Goutagny, Isabelle Treilleux, Aurélien Marabelle, Jean-Yves Blay, Christophe Caux, Nathalie Bendriss-Vermare. The antimicrobial peptide LL37 activates plasmacytoid dendritic cells in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1109. doi:10.1158/1538-7445.AM2014-1109