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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224323
A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses
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Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-derived MCL spheroids (MCL-PDLS) that recapitulate tumor oncogenic pathways and immune microenvironment in a multiplexed system that allows easy drug screening, including immunotherapies. MCL spheroids, integrated by tumor B cells, monocytes and autologous T-cells self-organize in disc-shaped structures, where B and T-cells maintain viability and proliferate, and monocytes differentiate into M2-like macrophages. RNA-seq analysis demonstrated that tumor cells recapitulate hallmarks of MCL-LN (proliferation, NF-kB and BCR), with T cells exhibiting an exhaustion profile (PD1, TIM-3 and TIGIT). MCL-PDLS reproduces in vivo responses to ibrutinib and demonstrates that combination of ibrutinib with nivolumab (anti-PD1) may be effective in ibrutinib-resistant cases by engaging an immune response with increased interferon gamma and granzyme B release. In conclusion, MCL-PDLS recapitulates specific MCL-LN features and in vivo responses to ibrutinib, representing a robust tool to study MCL interaction with the immune TME and to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.
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ARAUJO AYALA, Ferran, DOBAÑO-LÓPEZ, Cèlia, GARCIA VALERO, Juan, NADEU PRAT, Ferran, GAVA, Fabien, FARIA, Carla, NORLUND, Marine, MORIN, Renaud, BERNES-LASSERRE, Pascale, SERRAT AYMERICH, Neus, PLAYA-ALBINYANA, Heribert, GIMÉNEZ MARTÍNEZ, Rubén, CAMPO GÜERRI, Elias, LAGARDE, Jean-michel, LÓPEZ GUILLERMO, Armando, GINÉ SOCA, Eva, COLOMER PUJOL, Dolors, BEZOMBES, Christine, PÉREZ GALÁN, Patricia. A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses. _Leukemia_. 2023. Vol. 37, núm. 6, pàgs. 1311-1323. [consulta: 25 de novembre de 2025]. ISSN: 0887-6924. [Disponible a: https://hdl.handle.net/2445/224323]