Dissertation/ Thesis
Study of homeostatic interactions between dendritic cells, effector and regulatory lymphocytes on anti-tumor immune responses : study of the role of different dendritic cells in vivo in mice, and algorithmic study of the complex relationships between tumoral transcriptome, immune populations and survival in silico in patients ; Effet des interactions homéostatiques entre cellules dendritiques, lymphocytes effecteurs et régulateurs sur les réponses immunitaires anti-tumorales : étude du rôle de différentes cellules dendritiques in vivo chez la souris, et étude algorithmique des relations complexes entre transcriptome tumoral, populations immunitaires et survie in silico chez les patients
| العنوان: | Study of homeostatic interactions between dendritic cells, effector and regulatory lymphocytes on anti-tumor immune responses : study of the role of different dendritic cells in vivo in mice, and algorithmic study of the complex relationships between tumoral transcriptome, immune populations and survival in silico in patients ; Effet des interactions homéostatiques entre cellules dendritiques, lymphocytes effecteurs et régulateurs sur les réponses immunitaires anti-tumorales : étude du rôle de différentes cellules dendritiques in vivo chez la souris, et étude algorithmique des relations complexes entre transcriptome tumoral, populations immunitaires et survie in silico chez les patients |
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| المؤلفون: | Régnier, Paul |
| المساهمون: | Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité, Guillaume Darrasse-Jèze |
| المصدر: | https://theses.hal.science/tel-03411100 ; Immunologie. Université Sorbonne Paris Cité, 2018. Français. ⟨NNT : 2018USPCB133⟩. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Antigen-presenting cell, APC, Dendritic cell, DC, Homeostasis, NK, Tumor, Tumour, Transcriptome, Gene signature, Survival, Mouse, Human, Effector T lymphocyte, Regulatory T lymphocyte, Teffs, Th, Tregs, Flt3l, Flt3-L, FL, B16, Melanoma, B16-Fl, RhFL, Algorithm, Bioinformatics, Cancer, TCGA |
| الوصف: | The cancer, one of the main causes of death in the world, can appear in almost any type of tissue, and is characterized by an anarchic proliferation of cells and the establishment of a tolerogenic immune response favouring the tumour growth, leading to low efficiency of drug interventions. Dendritic cells (DCs), real sentinels of the body, seem to play a role in the establishment of both efficient anti-tumoral immune response and tolerance against cancer. Nevertheless, the role of the different DCs subtypes in the tumoral development stays poorly known. During this thesis, I studied different dendritic and lymphocytic cellular actors, their relationships and their involvement in the immune response or tolerance to tumours. During the first part of my thesis, I studied the effect of the artificial modulation of DCs homeostasis on other immune cells and also on anti-tumoral response in vivo in mice. I proved the existence of a paradoxical role of the Flt3-L (FL) cytokine - a growth factor essential to the differentiation and the homeostasis of classical/conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) - on the B16 melanoma growth. In fact, its overexpression or absence both lead to a better control of the tumoral development, accompanied by an increased survival of mice. FL deficiency induces, together with the loss of both cDCs and pDCs, a drastic reduction of regulatory T lymphocytes (Tregs) protecting the tumour, and also a global reinforcement of the anti-tumoral adaptive immune response via helper T lymphocytes. Its overexpression induces an increase of the numbers of cDCs and pDCs, and despite a raised presence of Tregs, also a strong intra-tumoral recruitment of activated natural killer (NK) cells, one of the major actors of the anti-tumoral innate response. The study of cDCs-deficient mice allowed me to demonstrate the existence of a DCs-mediated control of the NK cells homeostasis. Furthermore, the combination of both FL treatment and antibody-mediated Tregs depletion has an ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | French |
| Relation: | NNT: 2018USPCB133; tel-03411100; https://theses.hal.science/tel-03411100; https://theses.hal.science/tel-03411100/document; https://theses.hal.science/tel-03411100/file/va_Regnier_Paul.pdf |
| الاتاحة: | https://theses.hal.science/tel-03411100 https://theses.hal.science/tel-03411100/document https://theses.hal.science/tel-03411100/file/va_Regnier_Paul.pdf |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.9D2CA0DA |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |