ArticleOncogene2017
Increased FcγRIIB dominance contributes to the emergence of resistance to therapeutic antibodies in chronic lymphocytic leukaemia patients.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Unmasking FCGR2B as a high-grade serous ovarian cancer specific marker of immune suppression and tumor progression through multi-omics mining.Translational oncology · 2026Article
- NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy.Frontiers in immunology · 2024Article
- Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023Review
- Prognostic significance of FCGR2B expression for the response of DLBCL patients to rituximab or obinutuzumab treatment.Blood advances · 2021Article
- HDAC7 is an actionable driver of therapeutic antibody resistance by macrophages from CLL patients.Oncogene · 2020Article
- Murine Cross-Reactive Nonneutralizing Polyclonal IgG1 Antibodies Induced by Influenza Vaccine Inhibit the Cross-Protective Effect of IgG2 against Heterologous Virus in Mice.Journal of virology · 2020Article
- PI3K-p110δ contributes to antibody responses by macrophages in chronic lymphocytic leukemia.Leukemia · 2020Article
- SIRPα Suppresses Response to Therapeutic Antibodies by Nurse Like Cells From Chronic Lymphocytic Leukemia Patients.Frontiers in immunology · 2020Article
- Flow cytometry-based assessment of direct-targeting anti-cancer antibody immune effector functions.Methods in enzymology · 2020Article
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Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to therapeutic antibodies in chronic lymphocytic leukaemia (CLL) is common. In this study, we show that therapeutic antibodies against CD62L (CD62L-Ab) or CD20 (obinutuzumab) were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADP) in primary cultures of CLL cells. CLL cells derived from patients with active disease requiring treatment displayed resistance to these antibodies, whereas patients with stable disease were sensitive. Using enrichment strategies and transcriptomic analyses, we show that antibody-dependent tumour cell killing was FcγR-dependent and mediated by macrophages. Moreover, we show that resistance cannot be attributed to total numbers or established subtypes of monocytes/macrophages, or the efficiency with which they bind an immune complex. Rather, ADCC/ADP resistance was due to reduced signalling activity through the activating FcγRs resulting in the transfer of dominance to the inhibitory FcγRIIb within macrophages. Most significantly, we show that resistance is an actionable event that could be reversed using inhibitors of FcγRIIb signalling in primary cultures of CLL cells that were previously insensitive to obinutuzumab or CD62L-Ab.
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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.