ArticleEMBO molecular medicine2019
The IL-6 signaling complex is a critical driver, negative prognostic factor, and therapeutic target in diffuse large B-cell lymphoma.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
- Discovery of CDK8/19 inhibitors as lead compounds for IL-6-dependent lymphoma enabled by the formal synthesis of cortistatin A.Science advances · 2026Article
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- In vivo production of an anti-HIV antibody in mice by non-viral gene knockin in primate hematopoietic stem and progenitor cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Dynamic changes in serum IL-6, TNF-Frontiers in medicine · 2026Article
- A comprehensive analysis of B symptoms reveals prognosis and heterogeneity across different sites of diffuse large B-cell lymphoma.Annals of hematology · 2025Article
- Tumoricidal potential of binary therapy in lymphoma: Role of DC-NK cross-talk and checkpoint inhibitors.Histology and histopathology · 2025Review
- Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model.Scientific reports · 2025Article
- IL-6R expression is an independent prognostic factor in high-grade serous ovarian cancer.BJC reports · 2025Article
- Tumor Microenvironment, Inflammation, and Inflammatory Prognostic Indices in Diffuse Large B-Cell Lymphomas: A Narrative Review.International journal of molecular sciences · 2025Review
- Bcor loss promotes Richter transformation of chronic lymphocytic leukemia associated with Notch1 activation in mice.Leukemia · 2025Article
- Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large B-cell lymphomas and regulates the pro-tumor microenvironment.Haematologica · 2025Article
- The Relationship Between IL-6 and IL-10 Expression Levels and the Prognosis in B-Cell Non-Hodgkin Lymphoma Patients Treated with R-CHOP.Journal of inflammation research · 2025Article
- Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL.Frontiers in immunology · 2025Review
- Editorial: Cytokines and chemokines in lymphoma.Frontiers in immunology · 2025Article
- Immune reconstitution and evolution of B-cell-stimulating cytokines after R-CHOP therapy for HIV-associated DLBCL.Blood advances · 2024Observational
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- Assessment and prognostic significance of a serum cytokine panel in diffuse large B‑cell lymphoma.Oncology letters · 2024Article
- B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren's Disease: A Pilot Monocentric Exploratory Study.International journal of molecular sciences · 2024Article
- Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma.Nature medicine · 2024Article
- Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact.Frontiers in cellular and infection microbiology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Interleukin-6 (IL-6) is a growth factor for normal B cells and plasma cell-derived malignancies. Here, we show that the IL-6 signaling pathway is also active in a subset of diffuse large B-cell lymphoma (DLBCL) patients with particularly poor prognosis. Primary DLBCL cells and DLBCL cell lines expressing IL-6R engraft and form orthotopic lymphomas in humanized mice that ectopically produce human IL-6, and in mice reconstituted with a human immune system. We show that a subset of DLBCL cases have evolved mechanisms that ensure constitutive activation of the IL-6 signaling pathway, i.e., the expression of both chains of the IL-6R, the expression of the cytokine itself, and the mutational inactivation of a negative regulator of IL-6 signaling, SOCS1. IL-6 signaling promotes MYC-driven lymphomagenesis in a genetically engineered model, and treatment with the IL-6R-specific antibody tocilizumab reduces growth of primary DLBCL cells and of DLBCL cell lines in various therapeutic settings. The combined results uncover the IL-6 signaling pathway as a driver and negative prognosticator in aggressive DLBCL that can be targeted with a safe and well-tolerated biologic.
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