Présentation de l'équipe

Team presentation and main achievements

The team LIB is localized in a dynamic Charles Mérieux campus gathering the second largest university hospital site in Lyon and the Gerland site where the CIRI is localized. The main reason for LIB to be installed in Lyon-Sud (University building) is the presence at a walking distance of the second largest clinical hematology department (clinics and laboratory) in France, the LYSARC (The Lymphoma Academic Research Organization) and the lymphoma-dedicated Carnot Institute CALYM lymphoma, both located at the European Lymphoma Institute (ELI) building.

Based on the long-standing history of excellence in clinical and translational research in hematology, with a specific focus on malignant lymphoma, our team has developed a strong partnership with the Hospices Civils de Lyon (HCL) that provide us with institutional and financial support. The clinical research is structured in the Hematology Department, with 14 dedicated staff members (study coordinators, clinical research associates, data managers, technician), working in close collaborations with all clinical and administrative partners of the HCL. The department plays a key role in the INCA labelled CLIP (early clinical trial platform) and Centre de Recherche Clinique Cancer (in collaboration with the Léon Bérard Cancer center) and is internationally recognized by academic and industry partners as one of the most active sites dedicated to lymphoma clinical trials in France. Altogether, about 200 patients each year participate to more than 50 academic (117 patients in 2020) or industry-sponsored (99 patients in 2020) clinical trials for lymphoid malignancies on site.

We also take advantage of a dynamic industrial environment with multiple initiatives to consolidate industrial / academic collaborations, such as the Lyonbiopôle biotech cluster and the lymphoma-dedicated Carnot Institute CALYM (https://experts-recherche-lymphome.org/calym/). This institute allows partnering at an international strategic level with key pharmaceutical or biotech companies developing activities in the lymphoma field. CALYM provides full support (management of technology transfer and management of intellectual property, in collaboration with INSERM transfer and other appropriate stakeholders) and facilitate direct collaborative focused projects as well as shared innovation programs.

Lymphoma stands as the 6 th most frequent cancer worldwide, with more than 110,000 new diagnoses and over 42,000 deaths in Europe every year. Significant progress has been made in deciphering the biology and pathology of these tumours: the updated WHO (World Health Organization) classification identifies at least 80 different lymphoma entities or subtypes (1). This reflects a marked heterogeneity based on the presumed cell of origin, with distinct immunological and molecular features, resulting in diverse clinical courses and treatment options. While anti-CD20 antibodies have strongly improved the outcome of patients with B-cell lymphomas, many challenges still remain. Therapy resistance is still the leading cause of death in T-cell and some aggressive B-cell lymphomas, and so-called indolent lymphomas (40% of lymphomas) remain incurable.

Several major scientific outcomes and collaborations have fostered a national and international visibility of our team:

• Description of a new NKT lymphoma entity by Laurent GENESTIER and its functional characterization (Bachy, J Exp Med 2016). This work was done in collaboration with Mitch Kronenberg (La Jolla Institute for Allergy and Immunology). In addition to these initial observations, we extended our work to the role bacteria and chronic infection in NKT lymphomagenesis (Robinot, Blood 2018) and further developed original of T-cell lymphoma models as a way to better understand their human counterparts.
• Emmanuel BACHY (MD, PhD, co-team leader of LIB) stay at Dr. Louis Staudt’s laboratory (NCI, Bethesda) has led to the implementation of new cutting-edge technologies (CRISPR/CAS9 and ATAC-seq) and to complete the T-cell related theme of the team with a thorough investigation of human T-cell lymphomas. He is also partner of a European TRANSCAN H2020 project: ERANET-PLL in collaboration with colleagues from Germany, Austria…
• The GWAS analyses performed in diffuse large B-cell lymphoma (DLBCL) achieved plenary recognition within a new collaboration with the international INTERLYM consortium conducted by the NCI: Hervé GHESQUIERES (MD, PhD, head of the clinical hematology department and PI of the team) rapidly established himself as a recognized researcher in this field (Cerhan, … Ghesquieres et al, co-primary authors, Nat Genet 2014; Ghesquières et al, J Clin Oncol 2015). A second program of GWAS on follicular lymphoma is ongoing with the support of PRT-K program from INCa.
• Large genomic and transcriptomic analyses of follicular lymphoma (FL) were conducted by Sarah HUET (PharmD, PhD, PI of the team) leading to the characterization of several signatures which enable a better understanding of the biology of this lymphoma and their association with patient’s outcome (Huet, Lancet Oncol 2018). This led to an international collaboration with key leaders in the field of lymphoma (Dr Elias Campo, Barcelona University Hospital, Spain; Dr James Cerhan, Mayo Clinic, USA). Several other molecular characterizations were performed and are currently pursued and allowed our group to be well recognized in that field (Huet, Nat Rev Cancer, 2018).
• A strong partnership has been set up with the MICMAC team (Pr Karin tarte, UMR INSERM U1236, Rennes, France) with the aim of deciphering the interplay between lymphoma cells and their microenvironnement (Roche-CALYM funding).