Le jeudi 11 avril 2024, Madame Marie ANCION, titulaire d'un Master en sciences biomédicales à finalité approfondie et d'un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Madame Pascale HUBERT et de Monsieur Michaël HERFS.

Cette épreuve consistera en la défense publique d'une thèse intitulée : 

"Approach using «second generation» immune checkpoint inhibitors for the treatment of triple-negative breast cancer".

Le jury sera composé de :

Olivier PEULEN (Président), Bénédicte MACHIELSGuy BERCHEM (CH Luxembourg), Christine GILLES Michaël HERFS, Pascale HUBERT, Sophie LUCAS (UCLouvain), Thomas MARICHAL

Résumé de la thèse

Triple-negative breast cancer represents 10-20% of invasive breast cancers and has no specific treatment. The blockade of novel “second generation” immune checkpoints could be promising to enhance the number of responders to immunotherapy. This project aims at highlighting new immune checkpoints and to study the impact of their inhibition on TNBC progression. To this end, we selected potential immune checkpoints that showed high mRNA expression in TNBC using bioinformatic analyses. Next, we chose the targets displaying a higher protein expression in TNBC compared to the 3 other categories of breast cancer (LumA, LumB and HER2+) by using immunohistochemistry. The proteins VISTA, sirp-α, CD47 and PVR were selected. Several murine syngeneic tumor models were used. Checkpoint expression was thoroughly investigated in 12 specific immune populations. Monoclonal antibodies and inhibitors against said immune checkpoints were selected. Using syngeneic mouse models, the effect of the monoclonal antibodies on tumor growth as well as on composition of the immune tumor microenvironment was assessed. Notably, tumor growth was significantly slowed down in Balb/C mice bearing 4T1 tumors treated with anti-VISTA antibodies. Interestingly, anti-VISTA response seems to be mediated through a decrease in regulatory T cells and an enhanced M1-like/M2-like macrophages ratio.