Stromal cells regulate malignant B-cell spatial organization, survival, and drug response in a new 3D model mimicking lymphoma tumor niche

Lamaison, C.; Latour, S.; Helaine, N.; Le Morvan, V.; Monvoisin, C.; Mahouche, I.; Dussert, C.; Dessauge, E.; Pangault, C.; Seffals, M.; Broca-Brisson, L.; Alessandri, K.; Soubeyran, P.; Mourcin, F.; Nassoy, P.; Recher, G.; Tarte, K.; Bresson-Bepoldin, L.

doi:10.1101/2020.10.17.343657

bioRxiv · 10.1101/2020.10.17.343657

Stromal cells regulate malignant B-cell spatial organization, survival, and drug response in a new 3D model mimicking lymphoma tumor niche

Lamaison, C.·Latour, S.·Helaine, N.·Le Morvan, V.·Monvoisin, C.·Mahouche, I.·Dussert, C.·Dessauge, E.·Pangault, C.·Seffals, M.·Broca-Brisson, L.·Alessandri, K.·Soubeyran, P.·Mourcin, F.·Nassoy, P.·Recher, G.·Tarte, K.·Bresson-Bepoldin, L.

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Abstract

Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes as densely packed aggregates of tumor cells and their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. Until now, in vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B lymphomas remain scarce while all these parameters constitute key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on the encapsulation of cells inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D-model incorporating extracellular matrix and/or stromal cells. Lymphoma B cells and stromal cells dynamically formed self-organized 3D spheroids, thus initiating a coevolution of these two cell types, reflecting their bidirectional crosstalk, and recapitulating the heterogeneity of B-NHL subtypes. In addition, this approach makes it suitable to assess in a relevant in vitro model the activity of new therapeutic agents in B-NHL.

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Lamaison, C., Latour, S., Helaine, N., Le Morvan, V., Monvoisin, C., Mahouche, I., Dussert, C., Dessauge, E., Pangault, C., Seffals, M., Broca-Brisson, L., Alessandri, K., Soubeyran, P., Mourcin, F., Nassoy, P., Recher, G., Tarte, K., Bresson-Bepoldin, L.. 2020-10-17. Stromal cells regulate malignant B-cell spatial organization, survival, and drug response in a new 3D model mimicking lymphoma tumor niche. https://doi.org/10.1101/2020.10.17.343657

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