ArticleCell death & disease2023
Supplementation with α-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Differentiation state affects PD-L1 expression in cutaneous melanoma: a systematic review.Cellular & molecular biology letters · 2026Pooled it
- From metabolic node to smart building block: α-Ketoglutarate-empowered biomaterials for programmable cell fate.Materials today. Bio · 2026Review
- DNMT3A/TET2-mediated epigenetic alteration in Type-1 diabetes dysregulates the haematopoiesis.Molecular biology reports · 2026Review
- Aging-Driven Immunosuppression: The Role of Tregs in the Ovarian Tumor Microenvironment.Aging cell · 2026Article
- The "Cold Tumor" to "Hot Tumor" transformation strategy for triple-negative breast cancer: from mechanism to clinical translation.Molecular and cellular biochemistry · 2026Review
- Multiomics Reveals Mitochondrial and Metabolic Perturbations Underlying Cyclotriphosphazene-Induced Lung Injury.Environment & health (Washington, D.C.) · 2026Article
- Alpha-ketoglutarate Potentiates IL-1β Production and Suppressive Mechanisms of Myeloid-Derived Suppressor Cells by Altering Redox Metabolism and Inducing Autophagy.International journal of biological sciences · 2026Article
- Vinburnine Sensitizes Radiotherapy Efficacy in Nasopharyngeal Carcinoma by Triggering Pyroptosis and Immune Responses via Activation of EDAR-NFκB Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Gut microbiota: a new factor modulating the immunizing potential of viral and cancer vaccines.Research square · 2025Article
- Metabolites as agents and targets for cancer immunotherapy.Nature reviews. Drug discovery · 2025Review
- Progress in understanding the regulatory mechanisms of immune checkpoint proteins PD-1 and PD-L1 expression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Metabolic Reprogramming in Melanoma: An Epigenetic Point of View.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Construction of lung adenocarcinoma subtype and prognosis model based on fatty acid metabolism-related genes.Discover oncology · 2025Article
- Death-ision: the link between cellular resilience and cancer resistance to treatments.Molecular cancer · 2025Review
- αKG-induced oxidative stress and mTOR inhibition as a therapeutic strategy for liver cancer.Medical oncology (Northwood, London, England) · 2025Article
- Recent advances in novel tumor immunotherapy strategies based on regulating the tumor microenvironment and immune checkpoints.Frontiers in immunology · 2025Review
- Review
- Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.Nature communications · 2024Article
- A method for predicting drugs that can boost the efficacy of immune checkpoint blockade.Nature immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG's function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.
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