ArticleThe Journal of experimental medicine2012
Disruption of SIRPα signaling in macrophages eliminates human acute myeloid leukemia stem cells in xenografts.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Expression of cluster of differentiation 47 (CD47) and signal regulatory protein alpha (SIRPα) as prognostic biomarkers and potentially therapeutic targets in esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2026Article
- Optimizing antibody stability and efficacy in CD47- SIRPα inhibition via computational approaches.Molecular diversity · 2025Article
- Epithelial cell competition is promoted by signaling from immune cells.Nature communications · 2025Article
- Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction.Frontiers in immunology · 2025Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Progress in cancer research on the regulator of phagocytosis CD47, which determines the fate of tumor cells (Review).Oncology letters · 2024Review
- Signaling pathways governing the behaviors of leukemia stem cells.Genes & diseases · 2024Review
- Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche.Nature communications · 2024Article
- Finding potential targets in cell-based immunotherapy for handling the challenges of acute myeloid leukemia.Frontiers in immunology · 2024Review
- Targeting L-Selectin Lymphocytes to Deliver Immunosuppressive Drug in Lymph Nodes for Durable Multiple Sclerosis Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Building on the backbone of CD47-based therapy in cancer: Combination strategies, mechanisms, and future perspectives.Acta pharmaceutica Sinica. B · 2023Review
- Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment.Molecular cancer · 2023Review
- The landscape overview of CD47-based immunotherapy for hematological malignancies.Biomarker research · 2023Review
- Article
- Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer.Frontiers in immunology · 2023Review
- TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content.Frontiers in immunology · 2023Article
- Modified exosomal SIRPα variants alleviate white matter injury after intracerebral hemorrhage via microglia/macrophages.Biomaterials research · 2022Article
- CDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia.Nature communications · 2022Article
- Are We Moving the Needle for Patients withCancers · 2022Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 6 countries.
Funding
Abstract
Although tumor surveillance by T and B lymphocytes is well studied, the role of innate immune cells, in particular macrophages, is less clear. Moreover, the existence of subclonal genetic and functional diversity in some human cancers such as leukemia underscores the importance of defining tumor surveillance mechanisms that effectively target the disease-sustaining cancer stem cells in addition to bulk cells. In this study, we report that leukemia stem cell function in xenotransplant models of acute myeloid leukemia (AML) depends on SIRPα-mediated inhibition of macrophages through engagement with its ligand CD47. We generated mice expressing SIRPα variants with differential ability to bind human CD47 and demonstrated that macrophage-mediated phagocytosis and clearance of AML stem cells depend on absent SIRPα signaling. We obtained independent confirmation of the genetic restriction observed in our mouse models by using SIRPα-Fc fusion protein to disrupt SIRPα-CD47 engagement. Treatment with SIRPα-Fc enhanced phagocytosis of AML cells by both mouse and human macrophages and impaired leukemic engraftment in mice. Importantly, SIRPα-Fc treatment did not significantly enhance phagocytosis of normal hematopoietic targets. These findings support the development of therapeutics that antagonize SIRPα signaling to enhance macrophage-mediated elimination of AML.
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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.