ArticleInternational journal of cancer2023
The tumor microenvironment drives NK cell metabolic dysfunction leading to impaired antitumor activity.
Article in International journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 34 citations in OpenAlex.
- Tumor-derived ITGB3 shapes a primed but functionally constrained NK cell state in breast cancer through HLA-E-NKG2A signaling.Molecular biology reports · 2026Article
- Multifunctional-engineered NK cells overcome tumor immunosuppression by combining PD-L1 and HLA-E targeting and endogenous IL15 production.Signal transduction and targeted therapy · 2026Article
- Natural Killer Cell Plasticity in Epithelial Ovarian Cancer and Their Therapeutic Implications.Cells · 2026Review
- Mitochondrial transfer between tumor and immune cells: a nexus of metabolic adaptation and immune dysfunction.Biomarker research · 2026Review
- Peptide-mediated immunomodulation of tumor microenvironment in triple-negative breast cancer: A comprehensive review.The Journal of pharmacology and experimental therapeutics · 2026Review
- Pathobiology and clinical significance of malignant pleural effusions.EMBO molecular medicine · 2026Review
- NK cell biomimetic MOF nanoplatform disrupts hypoxia adaption for complete tumor ablation.Journal of nanobiotechnology · 2026Article
- Therapeutic reprogramming of natural killer cells for solid tumors: expanding frontiers into rare and ultra-rare malignancies.Frontiers in molecular biosciences · 2026Review
- Natural killer cell-based immunotherapies for colorectal cancer: Current strategies, challenges, and future perspectives.World journal of gastroenterology · 2025Review
- Pancreatic cancer cells escape T/NK cell immune surveillance through the expressional separation of CD58.Journal for immunotherapy of cancer · 2025Article
- Cytokine-mediated regulation of immune cell metabolic pathways in the tumor microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Endoplasmic reticulum stress responses in anticancer immunity.Nature reviews. Cancer · 2025Review
- Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.Molecular cancer · 2025Review
- Impaired natural killer cell maturation in lung adenocarcinoma driven byTranslational lung cancer research · 2025Article
- Review
- The diversity of natural killer cell functional and phenotypic states in cancer.Cancer metastasis reviews · 2025Review
- TGF-β Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment.ImmunoTargets and therapy · 2025Article
- Application and prospects of genetic engineering in CAR-NK cell therapy.Frontiers in immunology · 2025Review
- Nanocarriers for Delivery of Anticancer Drugs: Current Developments, Challenges, and Perspectives.Pharmaceutics · 2024Review
- Harnessing innate immune pathways for therapeutic advancement in cancer.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NK cells represent key players capable of driving antitumor immune responses. However, the potent immunosuppressive activity of the tumor microenvironment (TME) may impair their effector function. Here, we strengthen the importance of metabolic interactions between NK cells and TME and propose metabolic dysfunction as one of the major mechanisms behind NK failure in cancer treatment. In particular, we described that TME has a direct negative impact on NK cell function by disrupting their mitochondrial integrity and function in pediatric and adult patients with primary and metastatic cancer. Our results will help to design new strategies aimed at increasing the NK cell antitumor efficacy by their metabolic reprogramming. In this regard, we reveal an unprecedented role of IL15 in the metabolic reprogramming of NK cells enhancing their antitumor functions. IL15 prevents the inhibitory effect of soluble factors present in TME and restores both the metabolic characteristics and the effector function of NK cells inhibited by exposure to malignant pleural fluid. Thus, we propose here that IL15 may be exploited as a new strategy to metabolically reprogram NK cells with the aim of increasing the efficacy of NK-based immunotherapy in a wide range of currently refractory adult and pediatric solid tumors.
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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.