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Gembloux Agro-Bio Tech (GxABT)
Gembloux Agro-Bio Tech (GxABT)
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Travail de fin d'études: Chemotherapy-mediated activation of DNA damage tolerance pathways to improve immunotherapy in pleural mesothelioma

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Martinet, Christophe ULiège
Promotor(s) : Willems, Luc ULiège ; Fontaine, Alexis ULiège
Date of defense : 31-Aug-2023 • Permalink : http://hdl.handle.net/2268.2/18290
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Title : Travail de fin d'études: Chemotherapy-mediated activation of DNA damage tolerance pathways to improve immunotherapy in pleural mesothelioma
Translated title : [fr] Activation des voies de tolérance aux dommages de l'ADN par la chimiothérapie pour améliorer l'immunothérapie dans le mésothéliome pleural
Author : Martinet, Christophe ULiège
Date of defense  : 31-Aug-2023
Advisor(s) : Willems, Luc ULiège
Fontaine, Alexis ULiège
Committee's member(s) : Purcaro, Giorgia ULiège
Schroyen, Martine ULiège
Fickers, Patrick ULiège
Twizere, Jean-Claude ULiège
Willems, Luc ULiège
Fontaine, Alexis ULiège
Danthine, Sabine ULiège
Language : English
Number of pages : 66
Keywords : [en] Mesothelioma
[en] Cancer
[en] Immunotherapy
[en] Chemotherapy
Discipline(s) : Human health sciences > Oncology
Life sciences > Biochemistry, biophysics & molecular biology
Institution(s) : Université de Liège, Liège, Belgique
Degree: Master en bioingénieur : chimie et bioindustries, à finalité spécialisée
Faculty: Master thesis of the Gembloux Agro-Bio Tech (GxABT)

Abstract

[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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  • Martinet, Christophe ULiège Université de Liège > Gembloux Agro-Bio Tech

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