Development of patient-derived lymphomoids with preserved tumor architecture for lymphoma therapy screening

Albert Santamaria-Martínez (), Justine Epiney, Divyanshu Srivastava, Daniele Tavernari, Marco Varrone, Dina Milowich, Igor Letovanec, Thorsten Krueger, Rafael Duran, Giovanni Ciriello, Anne Cairoli and Elisa Oricchio ()
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Albert Santamaria-Martínez: École Polytechnique Fédérale de Lausanne (EPFL)
Justine Epiney: École Polytechnique Fédérale de Lausanne (EPFL)
Divyanshu Srivastava: École Polytechnique Fédérale de Lausanne (EPFL)
Daniele Tavernari: École Polytechnique Fédérale de Lausanne (EPFL)
Marco Varrone: Swiss Cancer Center Léman
Dina Milowich: Hôpital du Valais
Igor Letovanec: Hôpital du Valais
Thorsten Krueger: CHUV
Rafael Duran: Centre Hospitalier Universitaire Vaudois (CHUV)
Giovanni Ciriello: Swiss Cancer Center Léman
Anne Cairoli: Centre Hospitalier Universitaire Vaudois (CHUV)
Elisa Oricchio: École Polytechnique Fédérale de Lausanne (EPFL)

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract The efficacy of anti-cancer therapies depends on the genomic composition of the tumor, its microenvironment, spatial organization, and intra-tumor heterogeneity. B-cell lymphomas are a heterogeneous group of tumors emerging from B-cells at different stages of differentiation and exhibiting tumor-specific interactions with the tumor microenvironment. Thus, the effect of drug treatments can be influenced by the tumor composition and functional interactions among immune cells. Here, we develop a platform to maintain small fragments of human lymphoma tissue in culture for several days, and use them to test response to small molecules. We collect 27 patient samples representative of different lymphoma subtypes, and establish ex vivo tissue fragments that retain histological, cellular, and molecular characteristics of the original tissue, here referred to as lymphomoids. Using lymphomoids, we test sensitivity to several clinically approved drugs in parallel and examine tissue remodeling upon treatment. Moreover, when this information is available, we show that the effect of the inhibitors observed in lymphomoids is consistent with the patients’ response in the clinic. Thus, lymphomoids represent an innovative ex vivo model to assess the effect of anti-cancer therapies while preserving the tissue structure and its components.

Date: 2024
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DOI: 10.1038/s41467-024-55098-w

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