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Dobaño-López, Cèlia; Valero, Juan García; Araujo-Ayala, Ferran; Nadeu, Ferran; Gava, Fabien; Faria, Carla; Norlund, Marine; Morin, Renaud; Bernes-Lasserre, Pascale; Arenas, Fabian; Grau, Marta; López, Cristina; López-Oreja, Irene; Serrat, Neus; Martínez-Farran, Ares; Hernández, Lluís; Playa-Albinyana, Heribert; Giménez, Rubén; Beà, Silvia; Campo, Elías; Lagarde, Jean-Michel; López-Guillermo, Armando; Magnano, Laura; Colomer, Dolors; Bezombes, Christine; Pérez-Galán, Patricia
Blood cancer journal (New York), 05/2024, Letnik: 14, Številka: 1Journal Article
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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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