Lymphoma B cells remodel bone marrow stromal cell organization and function to induce a supportive cancer-associated fibroblast network

Dessauge, E.; Brauge, B.; Leonard, S.; Roulois, D.; Monvoisin, C.; Lejeune, T.; Destin, J.; Jouan, F.; Llamas-Gutierrez, F.; Mourcin, F.; TARTE, K.

doi:10.1101/2023.09.26.559605

bioRxiv · 10.1101/2023.09.26.559605

Lymphoma B cells remodel bone marrow stromal cell organization and function to induce a supportive cancer-associated fibroblast network

Dessauge, E.·Brauge, B.·Leonard, S.·Roulois, D.·Monvoisin, C.·Lejeune, T.·Destin, J.·Jouan, F.·Llamas-Gutierrez, F.·Mourcin, F.·TARTE, K.

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Abstract

Bone marrow (BM) involvement is a common feature of lymphomas deriving from germinal-center B cells and is associated with a bad prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, in association with a remodeling of surrounding tumor microenvironment. Analysis of in vitro-expanded FL mesenchymal stromal cells (MSCs) revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms supporting the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not been yet identified. In the current work, we identified in the BM milieu of FL patients a deregulation of soluble and extracellular matrix (ECM) components reflecting inflammation and ectopic differentiation into lymphoid-like stromal cells. We reproduced the same alterations in a murine model of lymphoma B-cell xenograft where a scRNAseq approach identified LepRpos MSCs as specifically and progressively reprogramed by tumor B-cell invasion. Analysis of FL BM collected before and after treatment confirmed that BM niche was partly dependent on the continuous contact with tumor B cells. Altogether, this work shed new lights on the kinetic and mechanisms of BM stromal niche reshaping in B-cell lymphoma.

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Dessauge, E., Brauge, B., Leonard, S., Roulois, D., Monvoisin, C., Lejeune, T., Destin, J., Jouan, F., Llamas-Gutierrez, F., Mourcin, F., TARTE, K.. 2023-09-28. Lymphoma B cells remodel bone marrow stromal cell organization and function to induce a supportive cancer-associated fibroblast network. https://doi.org/10.1101/2023.09.26.559605

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