Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
20
09
2023
accepted:
20
03
2024
revised:
13
03
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
2
5
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38697976
doi: 10.1038/s41408-024-01041-7
pii: 10.1038/s41408-024-01041-7
doi:
Substances chimiques
Galectins
0
LGALS9 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
75Subventions
Organisme : EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)
ID : IMLINFO EFA281/16
Organisme : Fundació la Marató de TV3 (TV3 Marathon Foundation)
ID : TAIFOL 201933-30
Organisme : Generalitat de Catalunya (Government of Catalonia)
ID : 2021SGR01294
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : SAF2017/88275R
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PRE2018-083797
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : CB16/12/00334
Organisme : Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya (Department of Innovation, Education and Enterprise, Government of Catalonia)
ID : 2017SGR1009
Informations de copyright
© 2024. The Author(s).
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