ArticleFrontiers in immunology2022
Dual checkpoint blockade of CD47 and LILRB1 enhances CD20 antibody-dependent phagocytosis of lymphoma cells by macrophages.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Tebentafusp, a T cell engager, promotes macrophage reprogramming and in combination with IL-2 overcomes macrophage immunosuppression in cancer.Nature communications · 2025Trial
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- CD47 monoclonal antibody enhances the inhibitory effect of anti-HER2 chimeric antigen receptor macrophages on ovarian cancer.Oncology letters · 2026Article
- Targeting phagocytosis checkpoints for cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Unlocking the promise of innate biology through the HLA-G/ILT2/ILT4 pathway.Journal for immunotherapy of cancer · 2026Review
- Macrophages in tumors with downregulated MHC-I expression: emerging therapeutic opportunities and translational challenges.Clinical and experimental immunology · 2026Review
- Combination of Fc-Protein Engineering Strategies: Design and Evaluation of Antibody Effector Functions.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Macrophage phagocytosis checkpoints in DLBCL immunotherapy: an evidence-maturity framework from CD47 to CD200.Frontiers in oncology · 2026Review
- Targeting Myeloid Cells for Cancer Immunotherapy.Cancer immunology research · 2025Review
- Revelation of prognosis and tumor microenvironment of colorectal cancer based on genes related to antibody-dependent cellular phagocytosis and single-cell landscape.Clinical proteomics · 2025Article
- Emerging therapeutics targeting tumor-associated macrophages for the treatment of solid organ cancers.Expert opinion on emerging drugs · 2025Review
- Targeting myeloid cells for hematological malignancies: the present and future.Biomarker research · 2025Review
- MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy.Cancer gene therapy · 2025Review
- A novel label-free method to determine equilibrium dissociation constants of antibodies binding to cell surface proteins.Scientific reports · 2025Article
- Evaluating TcAs for Use in Biotechnology Applications.Biotech (Basel (Switzerland)) · 2025Article
- Constructing Scissor+ risk model to predict prognosis and immunotherapy responses in PAAD by integrating bulk and single-cell RNA sequencing data.Frontiers in pharmacology · 2025Article
- The LILRB family in hematologic malignancies: prognostic associations, mechanistic considerations, and therapeutic implications.Biomarker research · 2024Review
- Blockade of the CD47/SIRPα checkpoint axis potentiates the macrophage-mediated antitumor efficacy of tafasitamab.Haematologica · 2024Article
- The relevance of tumor target expression levels on IgA-mediated cytotoxicity in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2024Article
- Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.Cancer communications (London, England) · 2024Review
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Authors and funding
21 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-dependent cellular phagocytosis (ADCP) by macrophages, an important effector function of tumor targeting antibodies, is hampered by 'Don´t Eat Me!' signals such as CD47 expressed by cancer cells. Yet, human leukocyte antigen (HLA) class I expression may also impair ADCP by engaging leukocyte immunoglobulin-like receptor subfamily B (LILRB) member 1 (LILRB1) or LILRB2. Analysis of different lymphoma cell lines revealed that the ratio of CD20 to HLA class I cell surface molecules determined the sensitivity to ADCP by the combination of rituximab and an Fc-silent variant of the CD47 antibody magrolimab (CD47-IgGσ). To boost ADCP, Fc-silent antibodies against LILRB1 and LILRB2 were generated (LILRB1-IgGσ and LILRB2-IgGσ, respectively). While LILRB2-IgGσ was not effective, LILRB1-IgGσ significantly enhanced ADCP of lymphoma cell lines when combined with both rituximab and CD47-IgGσ. LILRB1-IgGσ promoted serial engulfment of lymphoma cells and potentiated ADCP by non-polarized M0 as well as polarized M1 and M2 macrophages, but required CD47 co-blockade and the presence of the CD20 antibody. Importantly, complementing rituximab and CD47-IgGσ, LILRB1-IgGσ increased ADCP of chronic lymphocytic leukemia (CLL) or lymphoma cells isolated from patients. Thus, dual checkpoint blockade of CD47 and LILRB1 may be promising to improve antibody therapy of CLL and lymphomas through enhancing ADCP by macrophages.
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