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Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target
- Source :
- Blood Cancer Journal, Vol 14, Iss 1, Pp 1-14 (2024)
- Publication Year :
- 2024
- Publisher :
- Nature Publishing Group, 2024.
-
Abstract
- 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.
- Subjects :
- Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Subjects
Details
- Language :
- English
- ISSN :
- 20445385
- Volume :
- 14
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Blood Cancer Journal
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b316b5d0c4b44e859b070294d4e86f19
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41408-024-01041-7