Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223507
Title: Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target
Author: Dobaño-López, Cèlia
Garcia Valero, Juan
Araujo Ayala, Ferran
Nadeu, Ferran
Gava, Fabien
Faria, Carla
Norlund, Marine
Morin, Renaud
Bernes-Lasserre, Pascale
Arenas Ríos, Fabián
Grau, Marta
López González, Cristina
López Oreja, Irene
Serrat Aymerich, Neus
Martínez-Farran, Ares
Hernández Pous, Lluís
Playa-Albinyana, Heribert
Giménez Martínez, Rubén
Beà Bobet, Sílvia M.
Campo Güerri, Elias
Lagarde, Jean-Michel
López Guillermo, Armando
Magnano, Laura
Colomer Pujol, Dolors
Bezombes, Christine
Pérez-Galán, Patricia
Keywords: Limfomes
Càncer
Lymphomas
Cancer
Issue Date: 20-Mar-2024
Publisher: Springer Nature
Abstract: Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.
Note: Reproducció del document publicat a: https://doi.org/10.1182/blood.2024024251
It is part of: Blood Cancer Journal, 2024, vol. 14, num.1, p. 525-540
URI: https://hdl.handle.net/2445/223507
Related resource: https://doi.org/10.1182/blood.2024024251
ISSN: 2044-5385
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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