ArticleJournal of experimental & clinical cancer research : CR2023
Oxamate enhances the efficacy of CAR-T therapy against glioblastoma via suppressing ectonucleotidases and CCR8 lactylation.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 117 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- H4K12 Lactylation Impairs Dopaminergic Neuron Energy Metabolism via the HIF-1α/NDUFS1 Pathway in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Research progress of lactylation modification in tumors (Review).Experimental and therapeutic medicine · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Tumor microenvironment-responsive nanocarriers for enhanced glioblastoma immunotherapy.Journal of nanobiotechnology · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Identification ofTranslational cancer research · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- RILPL2 suppresses metabolic reprogramming and progression of cervical cancer by attenuating LDHA protein stability and inhibiting H3K18 lactylation.Cell death & disease · 2026Article
- Histone Lactylation in Immune Cells and Its Predictive Role in Sepsis Progression: A Prospective Observational Study.Shock (Augusta, Ga.) · 2026Observational
- [Research progress on protein lactylation modification in malignant tumors].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Review
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA.International journal of molecular sciences · 2026Review
- Metabolic reprogramming of CAR-T cells: a multi-pronged strategy to conquer the immunosuppressive tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundChimeric antigen receptor (CAR)-T immunotherapy fails to treat solid tumors due in part to immunosuppressive microenvironment. Excess lactate produced by tumor glycolysis increases CAR-T immunosuppression. The mechanism of lactate inducing the formation of immunosuppressive microenvironment remains to be further explored.
methodsImmunocyte subpopulations and molecular characteristics were analyzed in the orthotopic xenografts of nude mice using flow cytometry assay and immunohistochemical staining after oxamate, a lactate dehydrogenase A (LDHA) inhibitor, and control T or CAR-T cells injection alone or in combination. RT-qPCR, western blot, flow cytometry, immunofluorescence, luciferase reporter assay, chromatin immunoprecipitation and ELISA were performed to measure the effect of lactate on the regulation of CD39, CD73 and CCR8 in cultured glioma stem cells, CD4 + T cells or macrophages.
resultsOxamate promoted immune activation of tumor-infiltrating CAR-T cells through altering the phenotypes of immune molecules and increasing regulatory T (Treg) cells infiltration in a glioblastoma mouse model. Lactate accumulation within cells upregulated CD39, CD73 and CCR8 expressions in both lactate-treated cells and glioma stem cells-co-cultured CD4 + T cells and macrophages, and intracellular lactate directly elevated the activities of these gene promotors through histone H3K18 lactylation.
conclusionsUtilizing lactate generation inhibitor not only reprogramed glucose metabolism of cancer stem cells, but also alleviated immunosuppression of tumor microenvironment and reduced tumor-infiltrating CAR-Treg cells, which may be a potential strategy to enhance CAR-T function in glioblastoma therapy.
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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.