Presentation
Historically, the UMR U1236 was interested in the pathophysiology and microenvironment of B lymphoproliferations, a heterogeneous group of cancers with lymph node and/or medullary localization, the incidence of which has been steadily increasing over the last 40 years in developed countries and which constitutes a real public health issue. Recent genetic and histological mapping work underlines that lymphomagenesis is a complex multi-step process including early recurrent chromosomal translocations, additional genetic alterations and a strong interaction with a specialized microenvironment that evolves dynamically during tumor progression. More recently, the unit has been enriched by new themes such as acute lymphoblastic leukaemia, differentiation of the B lineage, regulation of genome or transcriptome changes of the B cell lineage as well as autoimmunity and inflammatory diseases. The models used range from in vitro (human cell lines and primary cultures) to in vivo (transgenic, syngeneic and xenograft mouse models) and clinical research.
The work of our unit focuses on the host/tumor dialogue within the tumor niche through complementary molecular and functional approaches. Our teams are also interested in the dialogue of these cells in a physiological context, as well as during inflammatory and/or autoimmune pathologies.
This project is based on close collaboration between biologists and clinicians and on the existence of a unique lymphoma tumor library supplied by an optimized tumor circuit.
Main research strategies
- The Characterization of the signals, signaling pathways, gene regulatory networks and epigenetic pathways involved in B-cell differentiation from early stages, through maturation in germinal centers, to terminal differentiation into plasma cells, since these mechanisms are impaired in B-cell lymphoid neoplasia.
- The Characterization of the functional heterogeneity and differentiation pathways of the supportive B cell microenvironment in healthy and pathological contexts, with specific interest in the interaction networks involving lymphoid stromal cells, T follicular helper cells (Tfh) and myeloid cells in B cell neoplasia and autoimmune inflammatory diseases.
- The exploration of the mechanisms and role of Ig gene rearrangements (classical or singular) and how their manipulation could provide innovative cellular tools for diagnosis and immunotherapy.
- The valorisation of our translational research work supported by industrial and academic programmes: i) the analysis of the mechanisms of action of new therapeutic strategies in B lymphomas in search of relevant biomarkers of activity; ii) the therapeutic use of mesenchymal stromal cells (MSCs); iii) the understanding and development of therapeutic approaches in acute and chronic inflammatory contexts; iv) innovative approaches to immunotherapy.
