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Article Dans Une Revue Blood Advances Année : 2021

A novel 3D culture model recapitulates primary FL B cell features and promotes their survival

Simon Latour
Laëtitia Andrique
Sylvain Baulande
Marine Seffals
Pierre Soubeyran
Jean-Philippe Merlio

Résumé

Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes as aggregates of tumor cells densely packed with their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. In vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B-cell lymphomas remain scarce, while all these parameters are key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on cell encapsulation inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D model incorporating lymphoma B cells, extracellular matrix (ECM), and/or tonsil stromal cells (TSC). Under 3D confinement, lymphoma B cells were able to form cohesive spheroids resulting from overexpression of ECM components. Moreover, lymphoma B cells and TSC dynamically formed self-organized 3D spheroids favoring tumor cell growth. 3D culture induced resistance to the classical chemotherapeutic agent doxorubicin, but not to the BCL2 inhibitor ABT-199, identifying this approach as a relevant in vitro model to assess the activity of therapeutic agents in B-NHL. RNA-sequence analysis highlighted the synergy of 3D, ECM, and TSC in upregulating similar pathways in malignant B cells in vitro than those overexpressed in primary lymphoma B cells in situ. Finally, our 3D model including ECM and TSC allowed long-term in vitro survival of primary follicular lymphoma B cells. In conclusion, we propose a new high-throughput 3D model mimicking lymphoma tumor niche and making it possible to study the dynamic relationship between lymphoma B cells and their microenvironment and to screen new anti-cancer drugs.
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Dates et versions

hal-03367891 , version 1 (27-10-2021)

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Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Claire Lamaison, Simon Latour, Nelson Hélaine, Valerie Le Morvan, Julien Saint-Vanne, et al.. A novel 3D culture model recapitulates primary FL B cell features and promotes their survival. Blood Advances, 2021, 5 (23), pp.5372-5386. ⟨10.1182/bloodadvances.2020003949⟩. ⟨hal-03367891⟩
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