ArticleJournal for immunotherapy of cancer2025
Lactylation-driven MVP upregulation boosts immunotherapy resistance by inhibiting PD-L1 degradation in hepatocellular carcinoma.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- 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
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Mitochondrial metabolism and PD-1 blockade: mechanisms and therapeutic opportunities in cancer immunotherapy.Molecular biology reports · 2026Review
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- A lactylation- and autophagy-associated prognostic signature reveals LSEC-derived CLEC3B as a novel mediator of hepatocellular carcinoma suppression.PLoS computational biology · 2026Article
- Review
- Core regulatory mechanisms of the PD-L1 axis and clinical strategies for immune escape and immunotherapy response in nasopharyngeal carcinoma.Translational oncology · 2026Review
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Cucurbitacin B Inhibits Hepatocellular Carcinoma by Inducing Ferroptosis and Activating the cGAS-STING Pathway.Current issues in molecular biology · 2026Article
- Integrative multi-omics profiling identifies a lactylation-associated, metabolically active, and immunosuppressive subtype of colon adenocarcinoma.Molecular & cellular oncology · 2026Article
- Post-translational modification in hepatocellular carcinoma resistance: molecular mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Drug resistance mechanisms of immunotherapy and translational strategies for reversing resistance for hepatocellular carcinoma: from bench to bedside.Frontiers in immunology · 2026Review
- Shikonin in Hepatocellular Carcinoma: Bridging Metabolic Disruption and Immunomodulation.Journal of hepatocellular carcinoma · 2026Review
- Article
- Targeting Lactylation for Cancer: Mechanisms, Effects, and Therapeutic Prospects.International journal of molecular sciences · 2025Review
- Lactylation: the malignant playbook of hepatocellular carcinoma cells and their roadmap to therapy resistance.Frontiers in immunology · 2025Review
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12 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is a prevalent malignancy and the third leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have emerged as first-line therapies for advanced HCC, substantially improving clinical outcomes. However, resistance to ICIs remains a major therapeutic challenge. Lactylation, a recently identified post-translational modification, has been implicated in tumor progression, although its role in ICIs resistance in HCC remains unclear.
methodsCytotoxicity assays, flow cytometry and orthotopic HCC mouse model were used to evaluate the effects of lactylation in remodeling the immune microenvironment. Chromatin immunoprecipitation sequencing and RNA sequencing were employed to identify lactylation-regulated gene profiles. Programmed cell death-ligand 1 (PD-L1) protein degradation was assayed by cycloheximide-chase analysis and ubiquitination assay. Interactions between major vault protein (MVP) and β-transducin repeat-containing protein (β-TrCP) were analyzed by co-immunoprecipitation experiments. Site-directed mutagenesis and truncation mutants were designed to determine binding sites of MVP-β-TrCP complex.
resultsElevated lactylation correlates with poor prognosis and ICIs resistance in patients with HCC. Inhibition of lactylation enhances CD8
conclusionsOur findings demonstrate that histone lactylation promotes ICIs resistance via MVP-dependent PD-L1 stabilization. Therefore, targeting lactylation in combination with programmed cell death protein-1/PD-L1 blockade offers a promising strategy to overcome immunotherapy resistance in HCC.
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