Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target
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), inc...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-05-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-024-01041-7 |
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| author | Cèlia Dobaño-López Juan García Valero Ferran Araujo-Ayala Ferran Nadeu Fabien Gava Carla Faria Marine Norlund Renaud Morin Pascale Bernes-Lasserre Fabian Arenas Marta Grau Cristina López Irene López-Oreja Neus Serrat Ares Martínez-Farran Lluís Hernández Heribert Playa-Albinyana Rubén Giménez Silvia Beà Elías Campo Jean-Michel Lagarde Armando López-Guillermo Laura Magnano Dolors Colomer Christine Bezombes Patricia Pérez-Galán |
| author_facet | Cèlia Dobaño-López Juan García Valero Ferran Araujo-Ayala Ferran Nadeu Fabien Gava Carla Faria Marine Norlund Renaud Morin Pascale Bernes-Lasserre Fabian Arenas Marta Grau Cristina López Irene López-Oreja Neus Serrat Ares Martínez-Farran Lluís Hernández Heribert Playa-Albinyana Rubén Giménez Silvia Beà Elías Campo Jean-Michel Lagarde Armando López-Guillermo Laura Magnano Dolors Colomer Christine Bezombes Patricia Pérez-Galán |
| author_sort | Cèlia Dobaño-López |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b316b5d0c4b44e859b070294d4e86f19 |
| institution | Kabale University |
| issn | 2044-5385 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj-art-b316b5d0c4b44e859b070294d4e86f192025-02-09T12:13:09ZengNature Publishing GroupBlood Cancer Journal2044-53852024-05-0114111410.1038/s41408-024-01041-7Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic targetCèlia Dobaño-López0Juan García Valero1Ferran Araujo-Ayala2Ferran Nadeu3Fabien Gava4Carla Faria5Marine Norlund6Renaud Morin7Pascale Bernes-Lasserre8Fabian Arenas9Marta Grau10Cristina López11Irene López-Oreja12Neus Serrat13Ares Martínez-Farran14Lluís Hernández15Heribert Playa-Albinyana16Rubén Giménez17Silvia Beà18Elías Campo19Jean-Michel Lagarde20Armando López-Guillermo21Laura Magnano22Dolors Colomer23Christine Bezombes24Patricia Pérez-Galán25Fundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerUniversité de Toulouse, INSERM, CNRS, Université de Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de ToulouseUniversité de Toulouse, INSERM, CNRS, Université de Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de ToulouseIMACTIV-3DIMACTIV-3DIMACTIV-3DFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerIMACTIV-3DFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerUniversité de Toulouse, INSERM, CNRS, Université de Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de ToulouseFundació de Recerca Clínic Barcelona - Institut d’Investigacions Biomèdiques August Pi i SunyerAbstract 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.https://doi.org/10.1038/s41408-024-01041-7 |
| spellingShingle | Cèlia Dobaño-López Juan García Valero Ferran Araujo-Ayala Ferran Nadeu Fabien Gava Carla Faria Marine Norlund Renaud Morin Pascale Bernes-Lasserre Fabian Arenas Marta Grau Cristina López Irene López-Oreja Neus Serrat Ares Martínez-Farran Lluís Hernández Heribert Playa-Albinyana Rubén Giménez Silvia Beà Elías Campo Jean-Michel Lagarde Armando López-Guillermo Laura Magnano Dolors Colomer Christine Bezombes Patricia Pérez-Galán Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target Blood Cancer Journal |
| title | Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target |
| title_full | Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target |
| title_fullStr | Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target |
| title_full_unstemmed | Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target |
| title_short | Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target |
| title_sort | patient derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin 9 as a novel immunotherapeutic target |
| url | https://doi.org/10.1038/s41408-024-01041-7 |
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