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Lymphomes Natural-Killer T Cells (NKT) : Impact Des Stimulations Antigéniques Chroniques Et Mécanismes De La Lymphomagénèse Remy Robinot

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Lymphomes Natural-Killer T Cells (NKT) : Impact Des Stimulations Antigéniques Chroniques Et Mécanismes De La Lymphomagénèse Remy Robinot Lymphomes Natural-Killer T cells (NKT) : impact des stimulations antigéniques chroniques et mécanismes de la lymphomagénèse Remy Robinot To cite this version: Remy Robinot. Lymphomes Natural-Killer T cells (NKT) : impact des stimulations antigéniques chroniques et mécanismes de la lymphomagénèse. Cancer. Université de Lyon, 2017. Français. NNT : 2017LYSE1255. tel-01744676 HAL Id: tel-01744676 https://tel.archives-ouvertes.fr/tel-01744676 Submitted on 27 Mar 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. N° d’ordre NNT : 2017LYSE1255 Année 2017 THESE de DOCTORAT DE L’UNIVERSITE DE LYON Opérée au sein de l’Université Claude Bernard Lyon 1 Ecole Doctorale N°340 (Biologie Moléculaire Intégrative et Cellulaire) Spécialité : Immunologie et Cancérologie Discipline : Biologie Soutenue publiquement le 05/12/2017 par Rémy Robinot LYMPHOMES NATURAL-KILLER T (NKT) : Impact des stimulations antigéniques chroniques et mécanismes de lymphomagenèse Directeur de thèse : Docteur Laurent Genestier Devant le jury composé de : Docteur Véronique Maguer-Satta, DR2 CNRS Présidente Professeur Philippe Lehours, PU-PH Université de Bordeaux Rapporteur Docteur Maria Leite de Moraes, DR1 CNRS Rapporteur Professeur Philippe Gaulard, PU-PH Université Paris Est Examinateur Docteur Sylvie Hermouet, MCU-PH Université de Nantes Examinatrice Professeur Germain Gillet, PU-PH Université de Lyon Examinateur Docteur Laurent Genestier, CR INSERM Directeur de thèse UNIVERSITE CLAUDE BERNARD - LYON 1 Président de l’Université M. le Professeur Frédéric FLEURY Président du Conseil Académique M. le Professeur Hamda BEN HADID Vice-président du Conseil d’Administration M. le Professeur Didier REVEL Vice-président du Conseil Formation et Vie Universitaire M. le Professeur Philippe CHEVALIER Vice-président de la Commission Recherche M. Fabrice VALLÉE Directrice Générale des Services Mme Dominique MARCHAND COMPOSANTES SANTE Faculté de Médecine Lyon Est – Claude Bernard Directeur : M. le Professeur G.RODE Faculté de Médecine et de Maïeutique Lyon Sud – Charles Mérieux Directeur : Mme la Professeure C. BURILLON Faculté d’Odontologie Directeur : M. le Professeur D. BOURGEOIS Institut des Sciences Pharmaceutiques et Biologiques Directeur : Mme la Professeure C. VINCIGUERRA Institut des Sciences et Techniques de la Réadaptation Directeur : M. X. PERROT Département de formation et Centre de Recherche en Biologie Humaine Directeur : Mme la Professeure A-M. SCHOTT COMPOSANTES ET DEPARTEMENTS DE SCIENCES ET TECHNOLOGIE Faculté des Sciences et Technologies Directeur : M. F. DE MARCHI Département Biologie Directeur : M. le Professeur F. THEVENARD Département Chimie Biochimie Directeur : Mme C. FELIX Département GEP Directeur : M. Hassan HAMMOURI Département Informatique Directeur : M. le Professeur S. AKKOUCHE Département Mathématiques Directeur : M. le Professeur G. TOMANOV Département Mécanique Directeur : M. le Professeur H. BEN HADID Département Physique Directeur : M. le Professeur J-C PLENET UFR Sciences et Techniques des Activités Physiques et Sportives Directeur : M. Y.VANPOULLE Observatoire des Sciences de l’Univers de Lyon Directeur : M. B. GUIDERDONI Polytech Lyon Directeur : M. le Professeur E.PERRIN Ecole Supérieure de Chimie Physique Electronique Directeur : M. G. PIGNAULT Institut Universitaire de Technologie de Lyon 1 Directeur : M. le Professeur C. VITON Ecole Supérieure du Professorat et de l’Education Directeur : M. le Professeur A. MOUGNIOTTE Institut de Science Financière et d'Assurances Directeur : M. N. LEBOISNE A Ludo Remerciements Je tiens tout d’abords à remercier Philippe Lehours et Maria Leite de Moraes d’avoir accepté d’être rapporteurs de ce travail de thèse. Merci à mes examinateurs, Philippe Gaulard, Sophie Hermouet et Germain Gillet. Merci à Véronique Maguer-Sata d’avoir accepté de présider ce jury. Laurent, Merci de m’avoir donné ma chance, malgré un « trou » dans mon CV, mon manque d’expérience technique en immunologie, et mon ignorance complète de la cancérologie. Je suis très heureux d’avoir passé ces 4 années sous ton encadrement. Merci pour ton enseignement et ta sympathie. J’espère avoir été à la hauteur, malgré tout. Désolé de m’être cassé le poignet ! Je suis très heureux également d’avoir pu vivre avec toi la création de ta propre équipe avec Gilles. Ce changement de laboratoire en cours de thèse aurait pu être déroutant, mais il s’est avéré plus que bénéfique pour mes 2 dernières années. C’est avec une certaine frustration que je dois clôturer ce chapitre « étudiant » de ma vie, un sentiment d’inachevé… Mais la frustration semble bien être une constante du monde de la recherche… il faut encore que je m’y fasse ! Espérons que parmi toutes les hypothèses que nous avons pu émettre ces dernier mois, au moins une s’avèrera vérifiable ! Encore une fois, merci pour tout. Je tiens à adresser mes remerciements tout particuliers à Thierry Defrance et Gilles Salles, m’ayant accueillit tour à tour dans leurs équipes respectives. Merci pour votre sympathie et votre accessibilité. Mirjam, We both arrived in the team during late 2013, we have been working together, almost just by 2 of us in the beginning, on this tricky project. We both lived very frustrating moments, but we hold on! I admire your great combativeness and I wish you the best for your future projects. For your support: Kiitos ! A mes compagnons de thèse : Ludo, Sylvain, Pascal, Antoine, Chien Cha, Alice, Seb… Sylvain, j’ai beaucoup appris grâce à toi durant ces 2 dernières années, que ce soit par ta formation médicale enrichissante ou par ton sérieux. Sache que j’admire ta façon de travailler. Manu, C’est à moi qu’est revenu la lourde tache de te succéder sur le projet lymphome NKT et de faire vivre ta découverte (même si on sait tous que c’est Lolo qui a fait les premiers marquages tétramères !). Être padawan après toi n’a pas été une mince affaire, tant Laurent semble t’admirer. J’ai beaucoup apprécié nos discussions depuis ton retour des US. Garde un œil sur ton bébé NKT ! Merci à toutes les personnes que j’ai côtoyé au sein du CIRI. La « Defrance team » : Morgan, Olivier, Maël, Dimitri, Paul, Helena, Mathilde, Nathalie… et toutes les personnes de la tour Cervi m’ayant filé un coup de main (Emilie, Cyril, Bariza, Antoine…). Merci à nos secrétaires de compet’ : Céline, Véronique et Christelle ! J’ai passé 2 super années en votre compagnie ! Puis est arrivé le moment du départ pour le CRCL et la « LGS team », 2 super années également ! Amel, merci pour ton aide très précieuse en particulier durant ces derniers mois difficiles. Merci Dimitri (encore !), Emilie (encore !!), Nathalie (et ses gâteaux élévateur de moral), Aurélie, pour votre aide technique et pas que ! Pierre, merci pour ton optimisme et tes nombreux conseils en biomol. Merci à Stéphanie, Jean-Pierre « mister PCR », Camille, Marc, Martine, Alexandra, Sandrine… Merci aux personnes des autres équipes de la plateforme CERVO: Nathalie pour la ddPCR, Celine pour la microscopie. Merci également aux personnes du CBS pour leur aide : Kaddour, Isabelle, Garance, Laurianne. Merci Professeur Benoit Jaulhac, de CNR des Borrelia pour sa collaboration. Merci à toutes les personnes avec qui j’ai pu correspondre pour préparer toutes ces manips à distance : Laurence, Lisa, Elody et Danièle. Sans votre réactivité, ce projet aurait difficilement pu se faire. Pour leur aide précieuse et leur disponibilité, je remercie les personnes des plateaux techniques, en particulier les membres du PBES (Nadine, Marie, Jean-François, Patrick, Jean-Louis, Pascaline, Agnès…) et du plateau de cytométrie (Thibault, Seb, Priscillia). Merci à Marie-Cécile Michallet et Anne Marie-Cardine, pour leur conseils tout au long des différents comités de suivit de thèse. Marie, les discussions que nous avons eues ont été un soutien moral précieux. Merci à ma famille et mes amis pour leur soutien sans faille, en particulier mes parents, toujours là pour moi, et mes pirates adorés de Toter Fisch, toujours compréhensifs vis à vis de la charge de travail que m’imposait la thèse. Merci à Nico, mon toupain colloc’ avec qui j’ai pu partager les joies et les déboires de la thèse, mais aussi les épreuves que la vie a mis en travers de nos chemins. Enfin, merci à Margaux, sans laquelle je n’y serais jamais arrivé. Les 6 derniers mois ont été autant difficile pour toi que pour moi, mais tu as tenu bon et m’a soutenu jusqu’au bout. J’ai de la chance de t’avoir. Ludo, Cela me paraît bien étrange de te remercier alors que tu n’es plus parmi nous… Mais je me dois de partager l’impact que tu as eu sur ces 4 années de ma vie. De collègues, nous sommes rapidement devenus amis. Nous avons partagé la science, notre passion pour le Metal, des bières, un groupe de musique, des concerts, des soirée jeux... Tu m’as appris beaucoup de choses au labo, notamment en cytométrie pour laquelle tu étais le référent officiel dans l’équipe. Ton organisation limite maniaque, ta curiosité et ton sens de la mise en forme étaient un exemple pour nous tous. Contrairement à moi, tu ne faisais jamais les choses à moitié.
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