ArticleScience advances2021
Lactate supports a metabolic-epigenetic link in macrophage polarization.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers, 1 of them a synthesis that pooled it.
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
193 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Cell-derived lactate triggers local hydrogelation and phenotype remodelling.Nature communications · 2026Article
- Review
- Review
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Injection site dictates the immune response to a biodegradable polymer and corresponding collagen regeneration.Bioactive materials · 2026Article
- AARS1-mediated lactylation reprograms macrophage lipid metabolism to restrict antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- Review
- Metabolic-epigenetic crosstalk in innate immune cell plasticity within the tumor microenvironment.Experimental & molecular medicine · 2026Review
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Lactate-induced H3K4me3 histone mark promotes PLOD1-driven prostate cancer invasion.Cell death & disease · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Integrative analysis of SEC13: a prognostic predictor and immunotherapeutic target.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Reverse cardio-oncology: neuroendocrine axis activation and cardiovascular-disease-derived factors synergistically remodel the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Aerobic exercise enhances α-tubulin lactylation and neurological recovery after ischemic stroke.Cell & bioscience · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
133 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
21 authors.
Funding
Abstract
Lactate accumulation is a hallmark of solid cancers and is linked to the immune suppressive phenotypes of tumor-infiltrating immune cells. We report herein that interleukin-4 (IL-4)–induced M0 → M2 macrophage polarization is accompanied by interchangeable glucose- or lactate-dependent tricarboxylic acid (TCA) cycle metabolism that directly drives histone acetylation, M2 gene transcription, and functional immune suppression. Lactate-dependent M0 → M2 polarization requires both mitochondrial pyruvate uptake and adenosine triphosphate–citrate lyase (ACLY) enzymatic activity. Notably, exogenous acetate rescues defective M2 polarization and histone acetylation following mitochondrial pyruvate carrier 1 (MPC1) inhibition or ACLY deficiency. Lastly, M2 macrophage–dependent tumor progression is impaired by conditional macrophage ACLY deficiency, further supporting a dominant role for glucose/lactate mitochondrial metabolism and histone acetylation in driving immune evasion. This work adds to our understanding of how mitochondrial metabolism affects macrophage functional phenotypes and identifies a unique tumor microenvironment (TME)–driven metabolic-epigenetic link in M2 macrophages.
Identifiers
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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.