ArticleThe Journal of clinical investigation2024
Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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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
86 citing papers in PubMed.
- Targeting the SELP/PSGL1 axis reprograms M2 macrophages and enhances anti-PD-1 efficacy in gastric cancer.Oncogene · 2026Article
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CBX3 aggravates nucleus pulposus cell apoptosis and extracellular matrix degradation in vitro via repressing SESN2-mediated mitophagy in an H3K9me3-dependent manner.Molecular biology reports · 2026Article
- Review
- Histone modifications: mechanisms, metabolic regulation, and therapeutic targeting in cancer.Precision clinical medicine · 2026Review
- Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.Molecular biology reports · 2026Review
- The intersection of chemokine signaling with the hallmarks of cancer in glioblastoma.Journal of neuro-oncology · 2026Review
- Single-Cell RNA Sequencing Reveals T-Cell Metabolic Activation and SGPL1 as a Candidate Predictor of PD-1 Resistance in Urothelial Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Metabolic Reprogramming and Neurotransmitter Signaling Co-Option in the Glioma Immune Microenvironment: Dual-Axis Regulation of Immunosuppression.Biomolecules · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Chromobox 3 assembles an epigenetic complex contributing to cystathionine γ-lyase-mediated protection against aortic aneurysm/dissection.Nature communications · 2026Article
- Homeobox B13 activates the hypoxia-inducible factor 1 pathway through histone lactylation thereby reprogramming lipid metabolism and promoting sorafenib resistance in hepatocellular carcinoma.Journal of cell communication and signaling · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Glioblastoma (GBM), an aggressive brain malignancy with a cellular hierarchy dominated by GBM stem cells (GSCs), evades antitumor immunity through mechanisms that remain incompletely understood. Like most cancers, GBMs undergo metabolic reprogramming toward glycolysis to generate lactate. Here, we show that lactate production by patient-derived GSCs and microglia/macrophages induces tumor cell epigenetic reprogramming through histone lactylation, an activating modification that leads to immunosuppressive transcriptional programs and suppression of phagocytosis via transcriptional upregulation of CD47, a "don't eat me" signal, in GBM cells. Leveraging these findings, pharmacologic targeting of lactate production augments efficacy of anti-CD47 therapy. Mechanistically, lactylated histone interacts with the heterochromatin component chromobox protein homolog 3 (CBX3). Although CBX3 does not possess direct lactyltransferase activity, CBX3 binds histone acetyltransferase (HAT) EP300 to induce increased EP300 substrate specificity toward lactyl-CoA and a transcriptional shift toward an immunosuppressive cytokine profile. Targeting CBX3 inhibits tumor growth by both tumor cell-intrinsic mechanisms and increased tumor cell phagocytosis. Collectively, these results suggest that lactate mediates metabolism-induced epigenetic reprogramming in GBM that contributes to CD47-dependent immune evasion, which can be leveraged to augment efficacy of immuno-oncology therapies.
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Registered trials
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