Therapeutic Immunotargeting of B Cells Tumours

JJFournié's Research Lab

Cancer Research Center of Toulouse

Loic Ysebaert : Biology & Therapeutic Targeting of Nurse-Like Cells in Chronic Lymphocytic Leukemia
Loic Ysebaert

Loic Ysebaert (MD. PhD.) investigates the phenotype, functions & druggability of Nurse-Like Cells in Chronic Lymphocytic Leukemia. This disease involves a constant immunosuppressive state, the development of progressively refractory disease, as defined by multiple relapses, and death mainly due to infections. The course of illness spreads over years, sometimes decades, because most of the patients only need watch and wait, until they deserve immuno-chemotherapy (see above) to block progression evidenced by adenopathy, hepatosplenomegaly or marrow failure.

Emilie Decaup & Loic Ysebaert

In the lymphoid organs, B-CLL cells are interspersed with normal stromal cells: endothelial cells, T cells and mesenchymal stem cells (MSC) in the bone marrow. Orchestration of intercellular signals between B-CLL cells and their microenvironment defines pseudo-follicles, where B-CLL cells are given key proliferation and survival cues. Among stromal cells, some peculiar monocyte-derived bystander cells, named "Nurse-Like Cells" (NLC), do supply B-CLL cells with important pro-survival cytokines. NLC have been detected in vitro, but much less is known about the precise role of NLC in the pathophysiology of the disease. This prompted Loic to address four important issues concerning these cells: do NLC correspond to B-CLL-specific tumor associated macrophages (TAMs), do they contribute to the characteristic immunosuppression of B-CLL patients, and finally do they cause an environment mediated-drug resistance (EM-DR)? On this latter point, Loic recently evidenced an active role of NLC in establishing therapeutic resistance to the main drugs used in B-CLL. The NLC and their interactions with B-CLL cells represent original targets for the screening and development of new drugs, in the aim of better clonal eradications and restoration of immune functions.

Left : Nurse-like cells mediating pseudoemperipolesis of smaller cells in culture;
Right : Distinctive transcriptome of nurse-like cells

Representative publications:
Ysebaert L, Gross E, Kuhlein E, Blanc A, Fournié JJ, Laurent G, Quillet-Mary A. Immune recovery after Fludarabine-Cyclophophamide-Rituximab treatment in B-chronic lymphocytic leukemia: implication for maintenance immunotherapy. Leukemia 2010 (in press).
Capietto AH, Keirallah S,, Gross E, Dauguet N, Laprévotte E, Jean C, Gertner-Dardenne J, Bezombes C, Quillet-Mary A, Poupot M, Ysebaert L, Laurent G , Fournié JJ, Emerging concepts for the treatment of hematological malignancies with therapeutic monoclonal antibodies. Current Drug Targets 2010 (in press).
De Toni F, Racaud-Sultan C, Chicanne G, Mas VM, Cariven C, Mesange F, Salles, JP, Manenti S, Ysebaert L. A crosstalk between the Wnt and the adhesion-dependent signaling pathways governs the chemosensitivity of acute myeloid leukemia. Oncogene. 2006 May 25; 25 (22):3113-22.