رسالة جامعية
Place of plasmacytoid dendritic cells in innate antitumoral immunity, from their activation by TLR ligands to their functionnality in context of melanoma ; Place des cellules dendritiques plasmocytoïdes dans l'immunité innée anti-tumorale, de leur activation par des ligands de TLR à leur fonctionnalité en contexte de mélanome
| العنوان: | Place of plasmacytoid dendritic cells in innate antitumoral immunity, from their activation by TLR ligands to their functionnality in context of melanoma ; Place des cellules dendritiques plasmocytoïdes dans l'immunité innée anti-tumorale, de leur activation par des ligands de TLR à leur fonctionnalité en contexte de mélanome |
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| المؤلفون: | Di Domizio, Jeremy |
| المساهمون: | Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph-Fourier - Grenoble I, Laurence Chaperot(laurence.chaperot@efs.sante.fr) |
| المصدر: | https://theses.hal.science/tel-00439353Test ; Immunologie. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨NNT : ⟩. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2009 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | cellule dendritique plasmocytoïde, TLR7, cancer, mélanome, signalisation, plasmacytoid dendritic cell, melanoma, signaling, [SDV.IMM]Life Sciences [q-bio]/Immunology |
| الوصف: | Several innovative therapeutic strategies for the treatment of cancer target Toll-like receptors (TLR) by using synthetic agonists. The most effective therapeutic agonists currently used mainly target TLR7 and -9. These TLRs are predominantly expressed by plasmacytoid dendritic cells (pDC). PDCs are key cells in the early immune response since they produce huge amounts of type I IFN and are able to cross-present antigens during viral infection, linking innate and adaptive immunity. Therefore, these cells constitute a subject of investigation for new antitumor immunotherapies development. The efficacy of treatments targeting TLR7 was demonstrated to involve activated pDCs. However, exact signaling pathways induced after TLR7 triggering and leading to the activation of human pDCs remain to be determined. Hence, we studied in a first part the signaling pathways induced by TLR7 ligands in human blood isolated pDCs and in the pDC cell line, GEN2.2 cells. This study allowed us to define a new signaling pathway leading to the rapid expression of IFN-stimulated genes (ISG) in the absence of type I IFN. In a second part, we determined if this particular pathway could be induced in TLR9-activated pDCs using two kinds of CpGs. We were also interested to identify the signaling factors responsible for the activation of this pathway by targeting the potential role of calcium. Finally, we characterized circulating dendritic cells in melanoma patients in order to verify that these cells are mobilizable and activable for TLR agonists based immunotherapy. This work reinforces the idea that pDCs constitute a target of choice for developing new antitumor therapeutic approaches. ; Plusieurs stratégies thérapeutiques innovantes dans le traitement du cancer ciblent les Toll-like receptor (TLR) par l'utilisation d'agonistes synthétiques dont les plus utilisés ciblent les TLR7 et -9. Ces TLR sont exprimés de façon prédominante par les cellules dendritiques plasmocytoïdes (pDC). Les pDC produisent de grandes quantités d'IFN de type I et ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | French |
| العلاقة: | tel-00439353; https://theses.hal.science/tel-00439353Test; https://theses.hal.science/tel-00439353/documentTest; https://theses.hal.science/tel-00439353/file/Manuscrit_These_corrigee.pdfTest |
| الإتاحة: | https://theses.hal.science/tel-00439353Test https://theses.hal.science/tel-00439353/documentTest https://theses.hal.science/tel-00439353/file/Manuscrit_These_corrigee.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.FB90A259 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |