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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/223507
Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target
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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.
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DOBAÑO-LÓPEZ, Cèlia, GARCIA VALERO, Juan, ARAUJO AYALA, Ferran, NADEU PRAT, 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. Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target. _Blood Cancer Journal_. 2024. Vol. 14, núm. 1, pàgs. 525-540. [consulta: 26 de novembre de 2025]. ISSN: 2044-5385. [Disponible a: https://hdl.handle.net/2445/223507]