ArticleOncotarget2015
Imprint of 5-azacytidine on the natural killer cell repertoire during systemic treatment for high-risk myelodysplastic syndrome.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
29 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Hypomethylating agents are the current therapy backbone for MDS and AML relapsing after allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2026Review
- T lymphocytes and natural killer cells in myelodysplastic syndromes: function, dysfunction, and therapeutic potential.Frontiers in immunology · 2026Review
- Modeling mesenchymal stromal cell support to hematopoiesis within a novel 3D artificial marrow organoid system.Scientific reports · 2025Article
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- CAR-NK cells: harnessing the power of natural killers for advanced cancer therapy.Frontiers in immunology · 2025Review
- Autoimmune diseases and myelodysplastic syndromes.Reumatologia · 2024Review
- The immunobiology of myelodysplastic neoplasms: a mini-review.Frontiers in immunology · 2024Review
- Effects of epigenetic therapy on natural killer cell function and development in hematologic malignancy.Journal of leukocyte biology · 2023Review
- Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models.The Journal of clinical investigation · 2023Article
- Epigenetic remodeling of the immune landscape in cancer: therapeutic hurdles and opportunities.Journal of biomedical science · 2023Review
- Epigenetic modulation and prostate cancer: Paving the way for NK cell anti-tumor immunity.Frontiers in immunology · 2023Review
- Epigenetic targeting to enhance acute myeloid leukemia-directed immunotherapy.Frontiers in immunology · 2023Review
- Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications.Diagnostics (Basel, Switzerland) · 2022Review
- Epi-immunotherapy for cancers: rationales of epi-drugs in combination with immunotherapy and advances in clinical trials.Cancer communications (London, England) · 2022Review
- Article
- Epigenetic regulation of natural killer cell memory.Immunological reviews · 2022Review
- Review
- Concentration-Dependent Decitabine Effects on Primary NK Cells Viability, Phenotype, and Function in the Absence of Obvious NK Cells Proliferation-Original Article.Frontiers in pharmacology · 2021Article
- Epigenetic Regulation of NK Cell-Mediated Antitumor Immunity.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-azacytidine (5-aza) is a hypomethylating agent approved for the treatment of high-risk myelodysplastic syndrome (MDS). It is assumed to act by demethylating tumor suppressor genes and via direct cytotoxic effects on malignant cells. In vitro treatment with hypomethylating agents has profound effects on the expression of killer-cell immunoglobulin-like (KIR) receptors on natural killer (NK) cells, as these receptors are epigenetically regulated via methylation of the promoters. Here we investigated the influence of 5-aza on the NK-cell repertoire during cytokine-induced proliferation in vitro and homeostatic proliferation in vivo in patients with high-risk MDS. In vitro treatment of NK cells from both healthy donors and MDS patients with low doses of 5-aza led to a significant increase in expression of multiple KIRs, but only in cells that had undergone several rounds of cell division. Proliferating 5-aza exposed NK cells exhibited increased IFN-γ production and degranulation towards tumor target cells. MDS patients had lower proportions of educated KIR-expressing NK cells than healthy controls but after systemic treatment with 5-aza, an increased proportion of Ki-67+ NK cells expressed multiple KIRs suggesting uptake of 5-aza in cycling cells in vivo. Hence, these results suggest that systemic treatment with 5-aza may shape the NK cell repertoire, in particular during homeostatic proliferation, thereby boosting NK cell-mediated recognition of malignant cells.
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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.