ArticleOncoimmunology2016
Loss of DNAM-1 ligand expression by acute myeloid leukemia cells renders them resistant to NK cell killing.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Genetically engineered hypoimmunogenic iPSCs: Strategies and considerations for clinical applications.Regenerative therapy · 2026Review
- Plasma membrane order maps functional diversity in immune cells.Nature chemical biology · 2026Article
- CD155 and its receptors in glioma: prospects for emerging immune checkpoint inhibitors.Acta neuropathologica communications · 2026Review
- The PVR-TIGIT/CD96/CD226 axis: a novel immune checkpoint target in ovarian cancer.Frontiers in immunology · 2026Review
- Immunotherapeutic strategies targeting the PVR-TIGIT/CD96/CD226 signaling pathway in glioma treatment.Annals of medicine · 2025Review
- A review of common immunotherapy and nano immunotherapy for acute myeloid leukemia.Frontiers in immunology · 2025Review
- RBM47 promotes cell proliferation and immune evasion by upregulating PDIA6: a novel mechanism of pancreatic cancer progression.Journal of translational medicine · 2024Article
- Immune checkpoint molecule DNAM-1/CD112 axis is a novel target for natural killer-cell therapy in acute myeloid leukemia.Haematologica · 2024Article
- STAT3 in acute myeloid leukemia facilitates natural killer cell-mediated surveillance.Frontiers in immunology · 2024Article
- A Novel Natural Killer Cell-related Gene Signature for Improving the Prediction of Prognosis and Immunotherapy Response in Bladder Cancer.Combinatorial chemistry & high throughput screening · 2024Article
- CAR-NK cells for acute myeloid leukemia immunotherapy: past, present and future.American journal of cancer research · 2023Review
- Natural killer cells and acute myeloid leukemia: promises and challenges.Cancer immunology, immunotherapy : CII · 2022Review
- Cytokine-enhanced cytolytic activity of exosomes from NK Cells.Cancer gene therapy · 2022Article
- The Multifaceted Role of STAT3 in NK-Cell Tumor Surveillance.Frontiers in immunology · 2022Review
- Genetic Engineering and Enrichment of Human NK Cells for CAR-Enhanced Immunotherapy of Hematological Malignancies.Frontiers in immunology · 2022Article
- New Orders to an Old Soldier: Optimizing NK Cells for Adoptive Immunotherapy in Hematology.Biomedicines · 2021Review
- DNAM-1/CD226 is functionally expressed on acute myeloid leukemia (AML) cells and is associated with favorable prognosis.Scientific reports · 2021Article
- Review
- Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future.Stem cell research & therapy · 2021Review
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is associated with poor natural killer (NK) cell function through aberrant expression of NK-cell-activating receptors and their ligands on tumor cells. These alterations are thought to promote formation of inhibitory NK-target cell synapses, in which killer cell degranulation is attenuated. Allogeneic stem cell transplantation can be effective in treating AML, through restoration of NK cell lytic activity. Similarly, agents that augment NK-cell-activating signals within the immunological synapse may provide some therapeutic benefit. However, the receptor-ligand interactions that critically dictate NK cell function in AML remain undefined. Here, we demonstrate that CD112/CD155 expression is required for DNAM-1-dependent killing of AML cells. Indeed, the low, or absent, expression of CD112/CD155 on multiple AML cell lines resulted in failure to stimulate optimal NK cell function. Importantly, isolated clones with low CD112/155 expression were resistant to NK cell killing while those expressing abundant levels of CD112/155 were highly susceptible. Attenuated NK cell killing in the absence of CD112/CD155 originated from decreased NK-target cell conjugation. Furthermore, we reveal by time-lapse microscopy, a significant increase in NK cell 'failed killing' in the absence of DNAM-1 ligands. Consequently, NK cells preferentially lysed ligand-expressing cells within heterogeneous populations, driving clonal selection of CD112/CD155-negative blasts upon NK cell attack. Taken together, we identify reduced CD155 expression as a major NK cell escape mechanism in AML and an opportunity for targeted immunotherapy.
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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.