Travail de fin d'études: Chemotherapy-mediated activation of DNA damage tolerance pathways to improve immunotherapy in pleural mesothelioma
Martinet, Christophe
Promoteur(s) : Willems, Luc ; Fontaine, Alexis
Date de soutenance : 31-aoû-2023 • URL permanente : http://hdl.handle.net/2268.2/18290
Détails
Titre : | Travail de fin d'études: Chemotherapy-mediated activation of DNA damage tolerance pathways to improve immunotherapy in pleural mesothelioma |
Titre traduit : | [fr] Activation des voies de tolérance aux dommages de l'ADN par la chimiothérapie pour améliorer l'immunothérapie dans le mésothéliome pleural |
Auteur : | Martinet, Christophe |
Date de soutenance : | 31-aoû-2023 |
Promoteur(s) : | Willems, Luc
Fontaine, Alexis |
Membre(s) du jury : | Purcaro, Giorgia
Schroyen, Martine Fickers, Patrick Twizere, Jean-Claude Willems, Luc Fontaine, Alexis Danthine, Sabine |
Langue : | Anglais |
Nombre de pages : | 66 |
Mots-clés : | [en] Mesothelioma [en] Cancer [en] Immunotherapy [en] Chemotherapy |
Discipline(s) : | Sciences de la santé humaine > Oncologie Sciences du vivant > Biochimie, biophysique & biologie moléculaire |
Institution(s) : | Université de Liège, Liège, Belgique |
Diplôme : | Master en bioingénieur : chimie et bioindustries, à finalité spécialisée |
Faculté : | Mémoires de la Gembloux Agro-Bio Tech (GxABT) |
Résumé
[en] Pleural mesothelioma is a rare and aggressive tumour originating from mesothelial cells of the pleura. For a long time, chemotherapy, sometimes combined with surgery and radiotherapy, has been the primary treatment option, though not definitively curative. Advances in immunotherapy have been and are being pursued. Particularly, one treatment involving the combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) has shown promising results in phases II and III of clinical trials. Moreover, this treatment has shown higher effectiveness in the presence of neoantigens. In this context, the aim of this master thesis is to use low-dose of chemotherapeutic agents to potentially generate neoantigens through DNA damage leading to mutations. This work highlighted that three chemotherapeutic treatments out of the five tested, namely the combination of cisplatin with pemetrexed, doxorubicin, and cyclophosphamide, could be good candidates. These exhibit a range of promising traits including a lack of substantial impact on cellular metabolism and apoptosis, induction of DNA damage, activation of repair and tolerance mechanisms for these impairments, increase of MHC-I expression, and enhancement of immune responses orchestrated by macrophages.
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