ArticleThe Journal of biological chemistry2016
Analysis of the Effects of the Bruton's tyrosine kinase (Btk) Inhibitor Ibrutinib on Monocyte Fcγ Receptor (FcγR) Function.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Using Informatics Tools to Identify Opportunities for Precision Medicine in Diffuse Large B-cell Lymphoma.Clinical lymphoma, myeloma & leukemia · 2020Pooled it
- From development to clinical success: the journey of established and next-generation BTK inhibitors.Investigational new drugs · 2025Review
- A genetically determined molecular switch modulates the anti-inflammatory potential of human IgA.Frontiers in immunology · 2025Article
- Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.Journal of neuroinflammation · 2024Article
- Inhibition of BET Proteins Regulates Fcγ Receptor Function and Reduces Inflammation in Rheumatoid Arthritis.International journal of molecular sciences · 2023Article
- Expression of Bruton´s tyrosine kinase in different type of brain lesions of multiple sclerosis patients and during experimental demyelination.Frontiers in immunology · 2023Article
- Clinical features and mutational analysis of X-linked agammaglobulinemia patients in Malaysia.Frontiers in immunology · 2023Article
- The Effect of BTK Inhibitor Ibrutinib on Leishmania infantum Infection In Vitro.Acta parasitologica · 2022Article
- Natural Killer Cells in Chronic Lymphocytic Leukemia: Functional Impairment and Therapeutic Potential.Cancers · 2022Review
- Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression?CNS drugs · 2022Review
- Disruption of Nurse-like Cell Differentiation as a Therapeutic Strategy for Chronic Lymphocytic Leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions.Allergy · 2022Review
- Article
- Current Perspectives: Evidence to Date on BTK Inhibitors in the Management of Multiple Sclerosis.Drug design, development and therapy · 2022Review
- Review
- Article
- [Antineoplasic drug repurposing in hematology for COVID-19 treatment].Bulletin du cancer · 2021Article
- Effective, safe, and sustained correction of murine XLA using a UCOE-BTK promoter-based lentiviral vector.Molecular therapy. Methods & clinical development · 2021Article
- Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets - Beyond B Lymphocytes.Frontiers in cell and developmental biology · 2021Review
- Current and novel BTK inhibitors in Waldenström's macroglobulinemia.Therapeutic advances in hematology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
The irreversible Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has shown efficacy against B-cell tumors such as chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma. Fcγ receptors (FcγR) on immune cells such as macrophages play an important role in tumor-specific antibody-mediated immune responses, but many such responses involve Btk. Here we tested the effects of ibrutinib on FcγR-mediated activities in monocytes. We found that ibrutinib did not affect monocyte FcγR-mediated phagocytosis, even at concentrations higher than those achieved physiologically, but suppressed FcγR-mediated cytokine production. We confirmed these findings in macrophages from Xid mice in which Btk signaling is defective. Because calcium flux is a major event downstream of Btk, we tested whether it was involved in phagocytosis. The results showed that blocking intracellular calcium flux decreased FcγR-mediated cytokine production but not phagocytosis. To verify this, we measured activation of the GTPase Rac, which is responsible for actin polymerization. Results showed that ibrutinib did not inhibit Rac activation, nor did the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester). We next asked whether the effect of ibrutinib on monocyte FcγR-mediated cytokine production could be rescued by IFNγ priming because NK cells produce IFNγ in response to antibody therapy. Pretreatment of monocytes with IFNγ abrogated the effects of ibrutinib on FcγR-mediated cytokine production, suggesting that IFNγ priming could overcome this Btk inhibition. Furthermore, in monocyte-natural killer cell co-cultures, ibrutinib did not inhibit FcγR-mediated cytokine production despite doing so in single cultures. These results suggest that combining ibrutinib with monoclonal antibody therapy could enhance chronic lymphocytic leukemia cell killing without affecting macrophage effector function.
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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.