ArticleNature immunology2025
Targeting lactylation reinforces NK cell cytotoxicity within the tumor microenvironment.
Article in Nature immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The trial behind it
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Who cites it
54 citing papers in PubMed.
- Advances in natural killer cell immunotherapy for hematologic malignancies.Cancer biology & therapy · 2026Review
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- CD112 Lactylation Drives Dual Immune Evasion From CD8+ T Cells and NK Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Metabolic reprogramming via LDHB confers resistance to lactate-induced dysfunction and enhanced antitumor activity in hiPSC-Derived NK cells.Stem cell reports · 2026Article
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Protein lactylation in cancer: principles, programmes and therapeutic opportunities.Molecular cancer · 2026Review
- Phytochemicals remodel antitumor immunity via the "microbiota-metabolite-receptor" axis: focus on colorectal cancer and immunotherapy.Medical oncology (Northwood, London, England) · 2026Review
- Lactate and lactylation in hepatocellular carcinoma: A new frontier in metabolic-epigenetic interactions.Medical oncology (Northwood, London, England) · 2026Review
- METTL5 reprograms glycolytic metabolism and promotes non-small cell lung cancer progression by modifying PGAM1.Oncology letters · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- SLPI/FBW7/c-Myc Axis Reduces Gemcitabine Sensitivity in PDAC by Enhancing Glycolysis and Impairing NK Cell Immunity.Cancer science · 2026Article
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- PARP inhibitors restore NK cell function via secretory crosstalk with tumor cells in prostate cancer.The Journal of clinical investigation · 2026Article
- Lactate-mediated NK cell dysfunction as a prognostic marker and therapeutic target in breast cancer.Cell death discovery · 2026Article
- Lactylation as a metabolic-epigenetic switch in cancer: dual roles in cell death resistance and therapeutic vulnerability.Cell death & disease · 2026Review
- Molecular and cellular landscapes of the immune microenvironment and multiomic biomarker-sets in platinum-resistant recurrent ovarian cancers.Journal of ovarian research · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Dysfunction of natural killer (NK) cells can be associated with tumor-derived lactate in the tumor microenvironment. Lactate-induced lysine lactylation (Kla) is a posttranslational modification, and strategies aimed at augmenting NK cell resistance to Kla might enhance cytotoxicity. Here we show that increased Kla levels in NK cells are accompanied by impaired nicotinamide adenine dinucleotide metabolism, fragmented mitochondria and reduced cytotoxicity. Supplementation with nicotinamide riboside (a nicotinamide adenine dinucleotide precursor) and honokiol (a SIRT3 activator) enhanced NK cell cytotoxicity by reducing cellular Kla levels. This combination restores antileukemic activity of NK cells in vivo and ex vivo by modulating Kla on ROCK1, thereby inhibiting ROCK1-DRP1 signaling to prevent mitochondrial fragmentation. Altogether, this study shows how lactylation can compromise NK cells and highlights this lactylation as a target for NK cell-based immunotherapy to enhance resilience to lactate in the tumor microenvironment.
Indexed as
Identifiers
40494934What OpenQuestion holds
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.