3D ex vivo platform for high‐throughput immunotherapy screening in relapsed/refractory lymphoma patients
Relapsed/refractory (R/R) B-cell lymphomas (B-NHL) remain incurable, with limited predictive biomarkers to guide immunotherapy. Preclinical platforms that faithfully preserve the immune context and the viability of patient samples are critically needed for relevant high-throughput drug testing. Here, we present a 3D ex vivo platform for immunotherapy screening that generates patient-derived lymphoma spheroids (PDLS) a scaffold- and matrix-free 3D model derived from peripheral blood or lymph node biopsies of patients, including R/R follicular lymphoma, transformed follicular lymphoma, or diffuse large B-cell lymphoma. PDLS maintain the cellular composition, T-cell activation, and immune escape profiles of the original tumors, supporting multiplexed screening of single-agent and combination therapies within clinically relevant time frames. This scalable model recapitulates immune-tumor cell interactions, provides rapid assessment of immunotherapy efficacy, and bridges preclinical research with clinical application in aggressive B-cell lymphomas. By integrating spatial profiling and single-cell RNA sequencing, PDLS can further evolve into patient-specific 3D tumor avatars that support precision oncology approaches in aggressive B-NHL.
Authors
- Sylvia Herter
- Peter‐Martin Bruch (ORCID: https://orcid.org/0000-0002-9992-3109)
- Loïc Ysebaert (ORCID: https://orcid.org/0000-0003-4102-7261)
- Pauline Gravelle (ORCID: https://orcid.org/0000-0002-0462-5652)
- Carla Faria (ORCID: https://orcid.org/0000-0001-9537-4758)
- Paul Marcoux (ORCID: https://orcid.org/0000-0002-4237-2668)
- Fanny Bouquet
- Christine Bezombes (ORCID: https://orcid.org/0000-0003-4079-4872)
- Fabien Gava (ORCID: https://orcid.org/0000-0003-1255-6121)
- Cathy Quelen (ORCID: https://orcid.org/0000-0003-0576-2234)
- Eugene Chiang
- Marie Tosolini (ORCID: https://orcid.org/0000-0001-5278-5952)
- Neus Serrat (ORCID: https://orcid.org/0000-0002-4970-8451)
- Patricia Pérez‐Galán (ORCID: https://orcid.org/0000-0003-3895-5024)
- Christina Schniederjohann (ORCID: https://orcid.org/0009-0001-2693-8086)
- Catia Fonseca
- S. Quertinmont
- Ron McCord
- Laura C. Deak
- Camille Laurent
- Juan G. Valero
Institutions
- Roche (Switzerland) (CH)
- European Molecular Biology Organization (DE)
- Inserm (FR)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Düsseldorf University Hospital (DE)
- Integrated Oncology (United States) (US)
- Institut universitaire du cancer de Toulouse Oncopole (FR)
- Laboratoire d'Aérologie (FR)
- The Lymphoma Academic Research Organisation (FR)
- Hospital Clínic de Barcelona (ES)
- Institut Claudius Regaud (FR)
- Lymphoma Study Association (FR)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Heinrich Heine University Düsseldorf (DE)
- University of Lausanne (CH)
Publication Details
- Journal
- HemaSphere
- Published
- 2026-09-01
- DOI
- https://doi.org/10.1002/hem3.70397
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- F. Hoffmann-La Roche
- Institut National de la Santé et de la Recherche Médicale
- Université de Toulouse
- Institut Carnot Santé Animale
- Genentech