Le jeudi 5 mars 2026,  Maureen CAMBIER présentera l'examen en vue de l’obtention du grade académique de Docteur en Sciences (Collège de doctorat en Biochimie, biologie moléculaire et cellulaire, bioinformatique et modélisation) sous la direction de Ingrid STRUMAN et Julien GUIOT.

Cette épreuve consistera en la défense publique d’une dissertation intitulée :

« Harnessing Exosomal Surface Proteins for the Detection and Targeting of Immune Evasion in Lung Cancer: A study on the Poliovirus Receptor ».

Le Jury sera composé de :

Mme C. SADZOT (Présidente), Mmes et MM. F. DEQUIEDT, J. GUIOT (Co-promoteur), C. JOSSE (Secrétaire), C. MICHIELS (UNamur), P. SAINTIGNY (Université Claude Bernard Lyon 1), I. STRUMAN (Promotrice).

Abstract

Although immunotherapy has revolutionized cancer treatment, understanding the mechanisms of resistance is essential to improving outcomes in lung cancer. Cells within the tumor microenvironment are constantly interacting with one another. This communication involves extracellular vesicles (EVs) that play a central role in tumor progression. The objective of this thesis was to investigate the role of EV-associated immune checkpoint proteins (ICPs) in immune escape and resistance to immunotherapy. Among these ICPs, PVR/CD155 is a transmembrane glycoprotein involved in interactions between tumor cells and immune cells, whose expression is associated with a more aggressive phenotype of lung cancer. In this context, this thesis aims to investigate the role of PVR/CD155 in immune evasion and resistance to immunotherapy in lung cancer.
 
We developed a multiplexed approach that enables the simultaneous detection of 18 immune checkpoint proteins on EV surfaces (EV-ICP) from a single liquid biopsy. Using this method, we profiled EV-ICP in plasma from healthy individuals and lung cancer patients undergoing immunotherapy, including a longitudinal study of responders and non-responders. The role of PVR associated with EV was further characterized and functionally investigated using in vitro and in vivo lung cancer models. 
 
The EV-ICP profiling revealed EV-associated PVR levels were significantly higher in lung cancer patients than in healthy controls and were highest in progressive disease, supporting a role in treatment resistance. Functional inhibition of PVR in human and murine lung cancer models reduced tumor cell proliferation and invasion, and tumor growth. In vivo, treatment with EVs lacking PVR resulted in reduced tumor growth and was associated with reduced PD-L1 expression in macrophages. These effects were recapitulated in vitro in bone-marrow-derived macrophages, demonstrating that exosomal PVR modulates macrophage phenotype.
 
 Altogether, these findings highlight exosomal PVR as a critical mediator of immune escape in lung carcinoma, modulating macrophage polarization and contributing to resistance to immunotherapy. The novel multiplexed detection approach enables comprehensive profiling of ICPs on EVs from liquid biopsy, offering a minimally invasive strategy to monitor tumor immune landscapes. Targeting EV-associated PVR may therefore represent a promising approach to overcome immunotherapy resistance and improve patient outcomes.