ArticleGut2025
Histone lactylation-driven feedback loop modulates cholesterol-linked immunosuppression in pancreatic cancer.
Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed.
- H4K12 Lactylation Regulates NDUFS7 to Drive Microglia Reverse Electron Transport in Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- KAT5-mediated HSPA1A lactylation drives immunotherapy resistance by inhibiting STAT1 degradation in esophageal squamous cell carcinoma.Oncogene · 2026Article
- Lactate-associated H3K18la upregulates RNF166 to promote immune evasion in hepatocellular carcinoma by remodeling c-Jun ubiquitination.Apoptosis : an international journal on programmed cell death · 2026Article
- Lactate-induced epithelial-mesenchymal transition: a metabolic nexus in pancreatic cancer metastasis.Translational cancer research · 2026Review
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Article
- Article
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Polyvinyl chloride promotes radioresistance in hepatocellular carcinoma by inhibiting radiotherapy-induced CD8⁺ T cell differentiation.Nature communications · 2026Article
- SMAD4 Palmitoylation Drives a Metabolic-Transcriptional Circuit to Promote Tumorigenesis and Confers Radiosensitivity in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Lactylation modification in extracellular vesicles: A key regulator of cellular communication.iScience · 2026Review
- Lactylation Converts ABHD6 into a Mitochondrial Regulator That Drives Lenvatinib Resistance in Hepatocellular Carcinoma.Cancer research · 2026Article
- HOXC9 enhances cholesterol metabolism and malignancy in pancreatic ductal adenocarcinoma through ITGA10/FAK/PI3K/CREB-dependent HMGCR activation.Journal of gastroenterology · 2026Article
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements.Journal of advanced research · 2026Review
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic cancer exhibits limited clinical responses to immunotherapy, highlighting the need for new strategies to counteract its immunosuppressive microenvironment. Although metabolic reprogramming and epigenetic changes contribute to malignancy, the impact of lactate-driven histone lactylation on the tumour microenvironment (TME) has not been fully explored.
objectiveThis study aims to investigate the role of histone lactylation in pancreatic cancer, focusing on its effects on cholesterol metabolism and antitumour immunity. DESIGNS: Global lactylome profiling was conducted to identify novel epigenetic mechanisms driven by lactate-induced histone lactylation. Mechanisms were investigated via RNA sequencing, CUT&Tag, immunoprecipitation-mass spectrometry and GST-pull down. Mass cytometry by time-of-flight,
resultsGlobal lactylome profiling revealed that lactate-driven histone lactylation, particularly H3K18la, promotes the transcriptional activation of ACAT2. ACAT2 acetylates mitochondrial carrier homolog 2 (MTCH2), stabilising it and disrupting oxidative phosphorylation, which increases lactate production and fuels a positive feedback loop in pancreatic cancer. This loop facilitates the delivery of cholesterol via small extracellular vesicles (sEVs), polarising tumour-associated macrophages toward an immunosuppressive M2 phenotype. Additionally, the PROTAC targeting ACAT2 enhanced the efficacy of immune checkpoint blockade therapy
conclusionsOur findings highlight the critical role of the H3K18la/ACAT2/sEV-cholesterol axis in TME reprogramming. Targeting this pathway may improve anti-PD-1 therapy response in pancreatic cancer, providing a novel therapeutic strategy by linking histone lactylation, cholesterol metabolic reprogramming and immune modulation.
Indexed as
Identifiers
What 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.