The immunoregulatory potential of endothelial cells in two lung diseases: cystic fibrosis & lung cancer – ImmunENDO

Despite major therapeutic progress in the treatment of lung cancer and cystic fibrosis, thanks in particular to immunotherapies and CFTR modulators, new hurdles are compromising patient survival. On the one hand, immunotherapies are facing resistance mechanisms that urge for the development of innovative models that take into account the tumor microenvironment and cellular heterogeneity. On the other hand, patients with cystic fibrosis are confronted with new emerging comorbidities such as a higher risk of developing cancers, the onset of which is not yet fully understood.
This project, based on human 2D and 3D models of multicellular tumor spheroids (MCTS), can address these needs by providing valuable information on how the different cellular compartments of the lung tumor microenvironment respond to the immuno/chemotherapy combination currently used as neoadjuvant therapy. In addition, by mimicking vascular perfusion using a microfluidic system, the vascularized MCTS model could represent a tumor ersatz relevant for future therapeutic developments. Finally, using our MCTS and a novel mouse model, we also plan to elucidate the role of CFTR during the physiological vascular development, in the tumor microenvironment and explain how a defect in CFTR expression can lead to the development of cancers in patients.