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Caractérisation des altérations fonctionnelles des cellules dendritiques plasmacytoïdes et myéloïdes dans les tumeurs mammaires murines

Abstract : Dendritic cells (DC) as professional antigen presenting cells, are key regulators of adaptive immune responses. Among them, plasmacytoid dendritic cells (pDC) are professional interferon producing cells critical for antiviral immunity but are also implicated in tolerance induction. In breast cancer, we previously reported that the pDC and regulatory T cells (Treg) infiltration in primary tumors represent independent prognostic factors associated with poor outcome. The current study was designed to understand this negative impact of tumor-associated pDC (TApDC). For this purpose, we have developed a murine mammary tumor model that closely mimic the human pathology, including TApDC and Treg infiltration associated with immune escape. We showed that tumor-associated myeloid DC (TAmDC) and TApDC are immature and preserve their ability to internalize antigens in vivo. Most importantly, TApDC are specifically altered for cytokine production in response to Toll-Like Receptor (TLR)-9 ligands while preserving unaltered response to TLR7 ligands. TAmDC spontaneously mature and produce large amounts of IL-10, but are unable to secrete IL-12. Finally both subsets are inhibited in their ability to activate CD4+ T cells. Alternatively, we showed that normal pDC are able to uptake apoptotic bodies from virally infected tumor cells. These results suggest that pDC and mDC are differentially altered in the tumor microenvironment. They further provide critical insights for developing new therapeutic strategies using TLR7 ligands to target TApDC activation in breast cancer
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Submitted on : Friday, October 25, 2013 - 10:47:31 AM
Last modification on : Saturday, November 5, 2022 - 4:00:16 AM
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  • HAL Id : tel-00876658, version 1

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Isabelle Le Mercier. Caractérisation des altérations fonctionnelles des cellules dendritiques plasmacytoïdes et myéloïdes dans les tumeurs mammaires murines. Médecine humaine et pathologie. Université Claude Bernard - Lyon I, 2009. Français. ⟨NNT : 2009LYO10229⟩. ⟨tel-00876658⟩

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