ArticleScience advances2024
Metabolic programs drive function of therapeutic NK cells in hypoxic tumor environments.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed.
- DRP1 depletion protects NK cells from hypoxia-induced dysfunction.Redox report : communications in free radical research · 2026Article
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- Review
- HIV tri-specific killer engagers directly enhance NK cell function and safely expand NK cells in vivo.Cell reports. Medicine · 2026Article
- Natural Killer Cell Immunotherapy in Solid Tumors: Microenvironmental Obstacles and Translational 3D Models.Biology · 2026Review
- Review
- Elevated lactate production exacerbates PM2.5-induced pulmonary fibrosis by stabilizing TGF-β1.Journal of advanced research · 2026Article
- Progress in cell-based immunotherapies for solid tumors.Discover oncology · 2026Review
- Functional segregation of HIF-1α and AhR controls NK cell responsiveness under hypoxia.iScience · 2026Article
- Mapping research trends in immune cell metabolic reprogramming in breast cancer: a parallel dual-database bibliometric study.Discover oncology · 2026Article
- Targeting metabolic reprogramming to enhance adoptive immunotherapy: emerging mechanisms and translational perspectives.Journal of translational medicine · 2026Review
- Engineering Bi-Specific CAR-NK Cells to Restore Antibody-Dependent Cellular Cytotoxicity in Solid Tumors.Cells · 2026Article
- Tumor immune microenvironment in non-small cell lung cancer progression.Frontiers in immunology · 2026Review
- Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-invasive Imaging Application.Cancer research and treatment · 2026Review
- Decoding the tumor microenvironment of triple-negative breast cancer: from immune evasion to precision immunotherapy.Frontiers in immunology · 2026Review
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
- Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.Research (Washington, D.C.) · 2026Article
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Bridging aging and colorectal cancer: synergistic roles of inflammaging and immunosenescence.Frontiers in immunology · 2026Review
- Challenges and opportunities of human iPSC-derived NK as "Off-the-shelf" cellular therapies.Journal of experimental & clinical cancer research : CR · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
Limited oxygen (hypoxia) in solid tumors poses a challenge to successful immunotherapy with natural killer (NK) cells. NK cells have impaired cytotoxicity when cultured in hypoxia (1% oxygen) but not physiologic (>5%) or atmospheric oxygen (20%). We found that changes to cytotoxicity were regulated at the transcriptional level and accompanied by metabolic dysregulation. Dosing with interleukin-15 (IL-15) enhanced NK cell cytotoxicity in hypoxia, but preactivation with feeder cells bearing IL-21 and 4-1BBL was even better. Preactivation resulted in less perturbed metabolism in hypoxia; greater resistance to oxidative stress; and no hypoxia-induced loss of transcription factors (T-bet and Eomes), activating receptors, adhesion molecules (CD2), and cytotoxic proteins (TRAIL and FasL). There remained a deficit in CD122/IL-2Rβ when exposed to hypoxia, which affected IL-15 signaling. However, tri-specific killer engager molecules that deliver IL-15 in the context of anti-CD16/FcγRIII were able to bypass this deficit, enhancing cytotoxicity of both fresh and preactivated NK cells in hypoxia.
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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.