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Theses

Les cellules dendritiques plasmacytoïdes dans le cancer à travers le rôle de TRAIL

Abstract : Plasmacytoid dendritic cells (PDC) represent a new distinct entity of dendritic cells. They are able to secrete high amounts of type I interferon upon viral exposure or stimulation by bacterial products such as CpG ODN due to their selective expression of Toll-like receptors (TLR)7 et 9.
Our laboratory has recently developed a PDC cell line (GEN2.2) derived from PDC leukemia (LPDC), which resist to conventional therapy. GEN2.2 share most of the phenotypic and functional features of normal PDC. We first used this cell line as a LPDC model and we show that they are sensitive to TRAIL (TNF-Related Apoptosis-Inducing Ligand)-induced apoptosis via the expression of the receptor DR5, like most of the LPDC, whereas normal PDC are not, allowing the setting of PDC leukaemia therapies using TRAIL agonists.
Normal PDC are difficult to isolate or to generate. We then used the GEN2.2 cell line as a normal PDC model. We thus discovered that these cells, once activated by TLR7 and 9 ligands, acquire a cytotoxic function via TRAIL expression and are able to kill tumoral cells. Therefore, PDC could play a crucial role in eradicating cancer, after activation.
Finally, we tried to specify the molecular mechanisms for TRAIL induction in PDC upon activation with TLR7 and 9 ligands.
Altogether, this work suggest that PDC could represent a key target in the development of new antitumoral therapeutic approaches.
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Theses
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https://tel.archives-ouvertes.fr/tel-00154726
Contributor : Ariane Blum <>
Submitted on : Thursday, June 14, 2007 - 3:13:18 PM
Last modification on : Friday, November 6, 2020 - 4:10:19 AM
Long-term archiving on: : Thursday, April 8, 2010 - 8:16:04 PM

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  • HAL Id : tel-00154726, version 1

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Citation

Ariane Blum. Les cellules dendritiques plasmacytoïdes dans le cancer à travers le rôle de TRAIL. Immunologie. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00154726⟩

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