ArticleThe Journal of clinical investigation2023
Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
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- Emergence of a mixed CAF population by FAP-CD3 T-cell engager limits therapeutic efficacy.Journal for immunotherapy of cancer · 2026Article
- Single cell profiling reveals malignant states and immune landscapes in PCNSL and systemic DLBCL.iScience · 2026Article
- LIFUS-driven engineered bacteria reprogram immunosuppressive niches via mechano-NOTCH signaling.Cell reports. Medicine · 2026Article
- Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma.Nature cancer · 2026Article
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- Immunometabolic Reprogramming of Fibroblastic Reticular Cells in the Tumor Immune Microenvironment.BioMed research international · 2026Review
- Metabolic reprogramming in tumor-associated cells of hematologic malignancies: mechanisms, crosstalk networks, and therapeutic implications in the tumor microenvironment.Frontiers in immunology · 2026Review
- Targeting NOP14 remodels the tumor immune microenvironment and enhances the antitumor efficacy of PD-1 blockade in DLBCL.Frontiers in immunology · 2026Article
- HIV-associated non-Hodgkin lymphoma tumor-microenvironment axes differ by EBV status across cellular origins.bioRxiv : the preprint server for biology · 2025Article
- Lymphoma B cells remodel bone marrow stromal cells into extracellular matrix-producing cancer-associated fibroblasts.Blood advances · 2025Article
- Multiplexed imaging mass cytometry elicits p-S6 as a therapeutic and prognostic factor in diffuse large B-cell lymphoma.Blood advances · 2025Article
- Novel signals for naive lymphocyte recruitment under inflammation.Molecular biomedicine · 2025Article
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- Angiogenesis-related gene signature for prognostic prediction and immune microenvironment characterization in diffuse large B-cell lymphoma.Clinical and experimental medicine · 2025Article
- Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration.Materials today. Bio · 2025Article
- Emerging strategies in lymph node-targeted nano-delivery systems for tumor immunotherapy.Essays in biochemistry · 2025Review
- Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.American journal of hematology · 2025Review
- Spatial transcriptomics reveals prognostically LYZCancer immunology, immunotherapy : CII · 2025Article
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31 authors at 11 institutions in 7 countries.
Funding
Abstract
Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast-activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD8+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD8+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.