ArticleJournal of immunology (Baltimore, Md. : 1950)2015
NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
What it found
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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
146 citing papers in PubMed, 235 citations in OpenAlex.
- Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial.Journal for immunotherapy of cancer · 2017Trial
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- Cancer Stem Cell Quiescence: Molecular and Microenvironmental Evidence for an Actively Regulated Adaptive Survival Strategy.Cancer medicine · 2026Review
- Natural Killer Cell Immunotherapy in Solid Tumors: Microenvironmental Obstacles and Translational 3D Models.Biology · 2026Review
- From T cell engagers to next-generation immune cell engagers for cancer immunotherapy.Antibody therapeutics · 2026Review
- Glioblastoma Stem Cells and Tumour Microenvironment: Interactions Across Hypoxia, Vasculature and Immune Modulation.International journal of molecular sciences · 2026Review
- Cancer Stemness and Dedifferentiation in Anaplastic Thyroid Carcinoma: Insights into a Multigenic, Microenvironmental Network and the Role of CD44.Biomedicines · 2026Review
- Therapeutic targeting of cancer stem cell-specific surface glycans and glycoproteins.Discover oncology · 2026Review
- Advancing osteosarcoma treatment: the impact of intratumoral metabolic reprogramming on immunotherapy.Frontiers in immunology · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Engineering CAR T NK and NKT cell therapies to target cancer stem cells and overcome stem like resistance.Discover oncology · 2025Review
- An Immunomodulating Peptide with Potential to Promote Anticancer Immunity Without Compromising Immune Tolerance.Biomedicines · 2025Article
- A Novel Class of Multi-substituted Diaryl Scaffold Derivatives Inhibit Glioblastoma Progression by Targeting CD155.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Cancer Stem Cells Connecting to Immunotherapy: Key Insights, Challenges, and Potential Treatment Opportunities.Cancers · 2025Review
- Killing the killers: Natural killer cell therapy targeting glioma stem cells in high-grade glioma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- NK-cell cytotoxicity toward pluripotent stem cells and their neural progeny: impacts of activating and inhibitory receptors and KIR/HLA mismatch.Stem cells (Dayton, Ohio) · 2025Article
- Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.International journal of biological sciences · 2025Review
- Enhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR.Clinical and translational medicine · 2025Article
- Single-cell transcriptomics reveals immunosuppressive microenvironment and highlights tumor-promoting macrophage cells in Glioblastoma.PloS one · 2025Article
86 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
14 authors at 3 institutions in 1 country.
Funding
Abstract
Increasing evidence supports the hypothesis that cancer stem cells (CSCs) are resistant to antiproliferative therapies, able to repopulate tumor bulk, and seed metastasis. NK cells are able to target stem cells as shown by their ability to reject allogeneic hematopoietic stem cells but not solid tissue grafts. Using multiple preclinical models, including NK coculture (autologous and allogeneic) with multiple human cancer cell lines and dissociated primary cancer specimens and NK transfer in NSG mice harboring orthotopic pancreatic cancer xenografts, we assessed CSC viability, CSC frequency, expression of death receptor ligands, and tumor burden. We demonstrate that activated NK cells are capable of preferentially killing CSCs identified by multiple CSC markers (CD24(+)/CD44(+), CD133(+), and aldehyde dehydrogenase(bright)) from a wide variety of human cancer cell lines in vitro and dissociated primary cancer specimens ex vivo. We observed comparable effector function of allogeneic and autologous NK cells. We also observed preferential upregulation of NK activation ligands MICA/B, Fas, and DR5 on CSCs. Blocking studies further implicated an NKG2D-dependent mechanism for NK killing of CSCs. Treatment of orthotopic human pancreatic cancer tumor-bearing NSG mice with activated NK cells led to significant reductions in both intratumoral CSCs and tumor burden. Taken together, these data from multiple preclinical models, including a strong reliance on primary human cancer specimens, provide compelling preclinical evidence that activated NK cells preferentially target cancer cells with a CSC phenotype, highlighting the translational potential of NK immunotherapy as part of a combined modality approach for refractory solid malignancies.
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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.