ArticleFrontiers in immunology2017
The CXCR4-STAT3-IL-10 Pathway Controls the Immunoregulatory Function of Chronic Lymphocytic Leukemia and Is Modulated by Lenalidomide.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- STAT3 as a Candidate Shared Regulator of the CXCR4/CXCL12 and CXCR5/CXCL13 Homing Axes in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2026Review
- CXCL2 is associated with IL-6/JAK2/STAT3 signaling and the immune microenvironment in lung squamous cell carcinoma.Functional & integrative genomics · 2026Article
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Functional differences between CLL- and ALL-derived CAR T cells in a 3D tumor microenvironment highlight CXCR4 and IL-10 as potential modulatory targets.HemaSphere · 2025Article
- Loss of STAT3 in acute myeloid leukemia favors tissue infiltration linked to CXCR4 signaling.Blood neoplasia · 2025Article
- Blocking secretion of exosomes by GW4869 dampens CD8Human cell · 2025Article
- Recent advances in CD5Annals of hematology · 2024Review
- Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma.Translational oncology · 2024Review
- Review
- BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia.JCI insight · 2024Article
- Molecular Mechanisms Driving IL-10- Producing B Cells Functions: STAT3 and c-MAF as Underestimated Central Key Regulators?Frontiers in immunology · 2022Article
- Article
- BTLA/HVEM Axis Induces NK Cell Immunosuppression and Poor Outcome in Chronic Lymphocytic Leukemia.Cancers · 2021Article
- SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.Nature communications · 2021Article
- Shared genomic segment analysis in a large high-risk chronic lymphocytic leukemia pedigree implicatesJournal of translational genetics and genomics · 2021Article
- T Cell Exhaustion and CAR-T Immunotherapy in Hematological Malignancies.BioMed research international · 2021Review
- Macrophage Polarization in Chronic Lymphocytic Leukemia: Nurse-Like Cells Are the Caretakers of Leukemic Cells.Biomedicines · 2020Review
- Targeting STAT3 in Cancer Immunotherapy.Molecular cancer · 2020Review
- New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM.Vaccines · 2020Review
- HDAC6 Inhibition Alleviates CLL-Induced T-Cell Dysfunction and Enhances Immune Checkpoint Blockade Efficacy in the Eμ-TCL1 Model.Frontiers in immunology · 2020Article
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) cells possess regulatory functions comparable to those of normal B10 cells, a regulatory B cell subset that suppresses effector T-cell function through STAT3-mediated IL-10 production. However, the mechanisms governing IL-10 production by CLL cells are not fully understood. Here, we show that the CXC chemokine ligand 12 (CXCL12)-CXCR4-STAT3 axis regulates IL-10 production by CLL cells and their ability to suppress T-cell effector function through an IL-10 mediated mechanism. Knockdown of STAT3 significantly impaired the ability of CLL cells to produce IL-10. Furthermore, experiments to assess the role of lenalidomide, an immunomodulatory agent with direct antitumor effect as well as pleiotropic activity on the immune system, showed that this agent prevents a CXCL12-induced increase in p-S727-STAT3 and the IL-10 response by CLL cells. Lenalidomide also suppressed IL-10-induced Y705-STAT3 phosphorylation in healthy T cells, thus reversing CLL-induced T-cell dysfunction. We conclude that the capacity of CLL cells to produce IL-10 is mediated by the CXCL12-CXCR4-STAT3 pathway and likely contributes to immunodeficiency in patients. Lenalidomide appears to be able to reverse CLL-induced immunosuppression through including abrogation of the CXCL12-CXCR4-S727-STAT3-mediated IL-10 response by CLL cells and prevention of IL-10-induced phosphorylation of Y705-STAT3 in T cells.
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