Le lundi 2 mars 2026, Madame Victoria MOHRING, titulaire d'un Master en sciences biomédicales à finalité approfondie et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiquese, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Madame Akeila BELLAHCENE.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "Implication of Methylglyoxal Stress in the Immunosuppressive Microenvironment of Triple-Negative Breast Cancer". 

Le jury sera composé de :

Thomas MARICHAL (Président), Nor Eddine SOUNNI (Secrétaire), Akeila BELLAHCENE, Guido BOMMER (UCLouvain), Christophe DEROANNE, Bastian HOCHST (Univ. München), Nathalie JACOBS.

Résumé de la thèse

Metabolic reprogramming via enhanced glycolysis is a hallmark of cancer, driving tumor progression and fostering pro-tumor immune responses. Methylglyoxal (MG), a reactive by-product of glycolysis, has recently gained attention as a potential oncometabolite. Our previous work linked MG stress to the progression and metastasis of triple-negative breast cancer (TNBC), yet its impact on the tumor immune microenvironment remains poorly defined. Using two preclinical breast cancer models, we demonstrate that MG stress is associated with the expansion of granulocytic myeloid-derived suppressor cells (g-MDSCs), key mediators of immune evasion. Notably, MG stress conferred metastatic capacity to non-metastatic 67NR breast tumors, a process potentially driven by NF-κB pathway activation, Gm-csf overexpression, and systemic g-MDSC expansion. 

In silico analyses revealed a positive correlation between MG stress-related gene signature and transcriptional markers of MDSC infiltration in TNBC patients. Furthermore, this signature distinguished anti-PD1 responders (low MG stress) from non-responders (high MG stress) in a cohort of melanoma patients. Collectively, these findings suggest that MG promotes an immunosuppressive tumor microenvironment that compromises immunotherapy efficacy. Dual targeting of MG stress, using carnosine, and PD1 signaling in the immunotherapy-resistant 4T1 breast cancer model significantly reduced the accumulation of g-MDSC and effectively prevented the development of lung metastases. These findings position MG stress as a therapeutically actionable contributor to immunosuppression and metastatic progression in TNBC.