Elise Dessauge (engineer); Baptiste Brauge (PhD student); Marion Guirriec (engineer); Simon Léonard, PhD (engineer); Cédric Ménard, PharmD PhD (assistant professor); Frédéric Mourcin, PhD (CR EFS)
FL development from normal GC B cells involves as genetic hallmarks: i) the founder
t(14;18) translocation associated with the deregulation of BCL2; ii) somatic mutations in histone modifier genes including KMT2D/MLL2, EZH2, and CREBBP. Of particular interest, some of the most frequent genetic hits in FL favor interactions with surrounding pro-tumoral non-B cells. In particular, inactivation of HVEM triggers a similar Tfh activation profile in both VavP-BCL2 FL mouse models and in FL patients (Boice, Salloul, Mourcin Cell 2016), suggesting that adequate genetically-engineered mouse models (GEMM) could be useful to decipher FL microenvironment subversion.
Importantly, besides the functional description of the dynamic FL tumor niche network, a major unsolved question remains the identification of the molecular mechanisms driving FL-microenvironment differentiation and polarization. FL stromal cells play a central role in FL pathogenesis through the direct activation of FL B cells, the indirect organization of the lymphoma-permissive cell niche, and probably the contribution to FL immune escape. Another key lymphoma-driver cell subset is Tfh. In particular, FL Tfh-derived IL-4 have been implicated in malignant B cell growth but also myeloid and stromal cell activation (Ame-Thomas Leukemia 2012; Amin Blood 2015; Pandey Blood 2017). The dynamic crosstalk between B cells, lymphoid stromal cells, and Tfh is thus considered as the core niche of FL pathogenesis.
Specific aims addressed in our project
Using human samples and original mouse models, our project aims at modeling and tracking the B-cell/stromal cell crosstalk considering kinetic and spatial heterogeneity with the objective to identify original therapeutic approaches. We thus address:
- Transcriptomic and spatial landscape of tumor microenvironment in human and mouse models of FL progression
- Functional consequences and targeting of the crosstalk between malignant B cells and their corrupted microenvironment
Research Engineer POSITION OPEN IN THE TEAM
We are looking for a highly dynamic Research engineer to start in our team.
All the details in the following link:Research engineer - (120.89 KB)