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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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