ArticleOncotarget2017
The Bruton's tyrosine kinase inhibitor ibrutinib exerts immunomodulatory effects through regulation of tumor-infiltrating macrophages.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 85 citations in OpenAlex.
- Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial.Annals of the rheumatic diseases · 2024Trial
- Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Pretreatment With BTK Inhibitors Improved the Sensitivity of DLBCL Cells to CAR-T Cells in a Coculture System by Downregulating the Polarisation of M2 Macrophages.Journal of cellular and molecular medicine · 2026Article
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Review
- Navigating the Complexities of Cancer Treatment-Induced Hypertension.Journal of cardiovascular development and disease · 2025Review
- Advancements in research on the cardiovascular toxicity caused by TEC family kinases inhibitors.Frontiers in pharmacology · 2025Review
- Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells.ImmunoHorizons · 2024Article
- Serum CXCL13 level is related to treatment response and predicts disease prognosis in Waldenström macroglobulinemia.Annals of hematology · 2024Article
- Article
- Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma.Frontiers in immunology · 2024Review
- Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension-Mechanisms and Mitigation.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications.Frontiers in cardiovascular medicine · 2023Review
- Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs.Frontiers in immunology · 2023Review
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- CXCL13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression.Journal of hematology & oncology · 2022Article
- The journey of CAR-T therapy in hematological malignancies.Molecular cancer · 2022Review
- A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib.BMC nephrology · 2022Article
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising efficacy in a variety of hematologic malignancies. However, the precise mechanism of action of the drug remains to be fully elucidated. Tumor-infiltrating macrophages presented in the tumor microenvironment have been shown to promote development and progression of B-cell lymphomas through crosstalk mediated by secreted cytokines and chemokines. Because Btk has been implicated in Toll-like receptor (TLR) signaling pathways that regulate macrophage activation and production of proinflammatory cytokines, we investigated the immunomodulatory effects of Btk inhibitor on macrophages. Our results demonstrate that Btk inhibition efficiently suppresses production of CXCL12, CXCL13, CCL19, and VEGF by macrophages. Furthermore, attenuated secretion of homeostatic chemokines from Btk inhibitor-treated macrophages significantly compromise adhesion, invasion, and migration of lymphoid malignant cells and even those not driven by Btk expression. The supernatants from Btk inhibitor-treated macrophages also impair the ability of endothelial cells to undergo angiogenic tube formation. Mechanistic analysis revealed that Btk inhibitors treatment downregulates secretion of homeostatic chemokines and cytokines through inactivation of Btk signaling and the downstream transcription factors, NF-κB, STAT3, and AP-1. Taken together, these results suggest that the encouraging therapeutic efficacy of Btk inhibitor may be due to both direct cytotoxic effects on malignant B cells and immunomodulatory effects on macrophages present in the tumor microenvironment. This novel mechanism of action suggests that, in addition to B-cell lymphomas, Btk inhibitor may also have therapeutic value in lymphatic malignancies and solid tumors lacking Btk expression.
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Registered trials
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.