ArticleFrontiers in immunology2023
Inhibiting efferocytosis reverses macrophage-mediated immunosuppression in the leukemia microenvironment.
Article in Frontiers in immunology, 2023. 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, 20 citations in OpenAlex.
- Spatial and Temporal Heterogeneity of Macrophage Efferocytosis in Tumors: Emerging Implications for Immunotherapy Biomarkers and Therapeutic Timing.Cancer medicine · 2026Review
- Metabolic pathways and chemotherapy resistance in acute myeloid leukemia (AML): Insights into Enoyl-CoA hydratase domain-containing protein 3 (Cancer pathogenesis and therapy · 2026Article
- A macrophage-related efferocytosis-based two-gene prognostic model for acute myeloid leukemia identified by multi-omics and machine learning.Annals of hematology · 2026Article
- Review
- A MERTK-Targeting Antibody-Drug Conjugate Selectively Depletes M2 Tumor-Associated Macrophages and MERTK-Expressing Cancer Cells.Cancer research · 2026Article
- Macrophage polarization in hematologic cancers: mechanisms and therapeutic strategies.Blood research · 2026Review
- Article
- Mitochondrial checkpoint for interferon responses in macrophages.Exploration of targeted anti-tumor therapy · 2026Review
- Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias.Haematologica · 2025Article
- Engineering Efferocytosis for Bone Regeneration.Macromolecular bioscience · 2025Review
- Genetic Insight Into Dissecting the FODMAP Diet Frame and Liver Cancer: The Mediation Role of Efferocytosis and Trogocytosis.Food science & nutrition · 2025Article
- ALOX15B-based efferocytosis clusters: prognostic implications and immune cell infiltration in breast cancer.Discover oncology · 2025Article
- Targeting myeloid cells for hematological malignancies: the present and future.Biomarker research · 2025Review
- Inflammation in atherosclerosis: pathophysiology and mechanisms.Cell death & disease · 2024Review
- Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin.International journal of molecular sciences · 2024Review
- MERTK Inhibition as a Targeted Novel Cancer Therapy.International journal of molecular sciences · 2024Review
- The intricate interplay between ferroptosis and efferocytosis in cancer: unraveling novel insights and therapeutic opportunities.Frontiers in oncology · 2024Review
- Aldehyde Dehydrogenase Genes as Prospective Actionable Targets in Acute Myeloid Leukemia.Genes · 2023Article
- Construction of an acute myeloid leukemia prognostic model based on m6A-related efferocytosis-related genes.Frontiers in immunology · 2023Article
- Unveiling efferocytosis-related signatures through the integration of single-cell analysis and machine learning: a predictive framework for prognosis and immunotherapy response in hepatocellular carcinoma.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Background: Previous studies show that the spleen and bone marrow can serve as leukemia microenvironments in which macrophages play a significant role in immune evasion and chemoresistance. We hypothesized that the macrophage driven tolerogenic process of efferocytosis is a major contributor to the immunosuppressive leukemia microenvironment and that this was driven by aberrant phosphatidylserine expression from cell turnover and cell membrane dysregulation. Methods: Since MerTK is the prototypic efferocytosis receptor, we assessed whether the MerTK inhibitor MRX2843, which is currently in clinical trials, would reverse immune evasion and enhance immune-mediated clearance of leukemia cells. Results: We found that inhibition of MerTK decreased leukemia-associated macrophage expression of M2 markers PD-L1, PD-L2, Tim-3, CD163 and Arginase-1 compared to vehicle-treated controls. Additionally, MerTK inhibition led to M1 macrophage repolarization including elevated CD86 and HLA-DR expression, and increased production of T cell activating cytokines, including IFN-β, IL-18, and IL-1β through activation of NF-κB. Collectively, this macrophage repolarization had downstream effects on T cells within the leukemia microenvironment, including decreased PD-1 Discussion: These results demonstrate that MerTK inhibition using MRX2843 altered the leukemia microenvironment from tumor-permissive toward immune responsiveness to leukemia and culminated in improved immune-mediated clearance of AML.
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Registered trials
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