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Rôle de TLR7 dans la progression tumorale dans le cancer du poumon

Marion Dajon 1
1 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
IGR - Institut Gustave Roussy, CRC - Centre de Recherche des Cordeliers
Abstract : Numerous studies have implicated some TLR in tumor development. Previously, we have demonstrated that lung tumor cells express TLR7, a receptor for ssRNA, and that high TLR7 expression confers to NSCLC patients bad clinical outcome. In mice models of lung cancer, we further demonstrated that the injection of TLR7 agonists led to a pro-tumoral effect.My thesis work has firstly demonstrated the mechanisms involved in the pro-tumoral effects of TLR7 in lung cancer: TLR7 stimulation on tumor cells induces a high production of CCL2 and GM -CSF, as well as a sharp MDSC recruitment within the tumor. These MDSC, by their immunosuppressive properties, are implicated in the pro-tumoral effect upon TLR7 stimulation. We also demonstrated that TLR7 stimulation was pro-metastatic in a mice model of lung cancer and that MDSC were also involved in this effect. These pro-metastatic effects associated with TLR7 have been confirmed in humans through the studies of transcripts and proteins involved in invasion, angiogenesis, Epithelial–mesenchymal transition and metastasis. Finally, we demonstrated that TLR7 ligands are present in tumor microenvironment of lung cancer patients and that intratumoral injection of respiratory viral infections such as IAV and RSV, have a pro-tumoral effect in lung cancer mice model. These respiratory viruses could therefore be at the origin of the overexpression of TLR7 and the poor clinical outcome associated with this receptor in lung cancer patients. This research has thus made possible to highlight new aggravating factors in lung cancer, including respiratory viruses, and to discover the mechanisms involved.
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Submitted on : Friday, October 4, 2019 - 1:01:22 AM
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Marion Dajon. Rôle de TLR7 dans la progression tumorale dans le cancer du poumon. Immunologie. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066272⟩. ⟨tel-02305243⟩



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