Gembloux Agro-Bio Tech (GxABT)
Gembloux Agro-Bio Tech (GxABT)

Activation of DNA damage tolerance pathways to improve immunotherapy treatment in malignant mesothelioma

Grégoire, Mélanie ULiège
Promotor(s) : Willems, Luc ULiège ; Fontaine, Alexis ULiège
Date of defense : 14-Jan-2022 • Permalink :
Title : Activation of DNA damage tolerance pathways to improve immunotherapy treatment in malignant mesothelioma
Translated title : [fr] Activation des mécanismes de tolérance de dommages à l'ADN pour améliorer les traitements d'immunothérapie du mésothéliome.
Author : Grégoire, Mélanie ULiège
Date of defense  : 14-Jan-2022
Advisor(s) : Willems, Luc ULiège
Fontaine, Alexis ULiège
Committee's member(s) : Sindic, Marianne ULiège
Hamaïdia, Malik ULiège
Schroyen, Martine ULiège
Deleu, Magali ULiège
Language : English
Number of pages : 73
Keywords : [en] Mesothelioma
[en] Cancer
[en] Immunotherapy
[en] Chemotherapy
Discipline(s) : Life sciences > Biochemistry, biophysics & molecular biology
Human health sciences > Oncology
Target public : Researchers
Professionals of domain
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)


[en] Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that affects the mesothelial cells of the pleura. Conventional treatments include surgery, radiation therapy and chemotherapy. In the vast majority of cases, none of these treatments is definitively curative. In this context, new approaches such as immunotherapy show promise. In particular, a treatment targeting the immune checkpoint inhibitors PD-1 and CTLA4 (nivolumab and ipilimumab, respectively) is effective against the sarcomatoid subtype of MPM. Furthermore, a positive correlation links the efficacy of PD-1 and CTLA4 immunotherapy with the presence of neoantigens. In this context, the aim of this master thesis is to use chemotherapy at sublethal doses to induce DNA damage and create new mutations potentially generating neoantigens. This work identified doxorubicin among a series of 7 preselected compounds, as a candidate exhibiting the targeted characteristics, namely: the absence of a significant effect on cell
metabolism and apoptosis, induction of DNA damage, the initiation of repair and tolerance mechanisms to these lesions and improvement of the immune response directed by macrophages.



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