ArticleFrontiers in oncology2021
Inhibition of LDH-A by Oxamate Enhances the Efficacy of Anti-PD-1 Treatment in an NSCLC Humanized Mouse Model.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 101 citations in OpenAlex.
- Research progress in metabolic reprogramming and targeting metabolic pathways for clear cell renal cell carcinoma.Genes & diseases · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Lactate signaling and immune suppression in tumors: mechanisms and therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Lactate metabolic reprogramming and lactylation modification: molecular mechanisms reshaping the tumor immunosuppressive microenvironment.Cell & bioscience · 2026Review
- [Research progress on protein lactylation modification in malignant tumors].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Review
- Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA.International journal of molecular sciences · 2026Review
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.Nature cell biology · 2026Article
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Post-translational modification networks in tumor radiosensitivity: mechanistic insights and therapeutic opportunities.Journal of translational medicine · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- The multifaceted functions of lactate and its translational potentials in cancer.Frontiers in pharmacology · 2026Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapy is a curable treatment for certain cancers, but it is still only effective in a small subset of patients, partly because of the lack of sufficient immune cells in the tumor. It is reported that targeted lactate dehydrogenase (LDH) to reduce lactic acid production can promote the infiltration and activity of immune cells and turn tumors into hot tumors. Therefore, we constructed a humanized mouse model to evaluate the efficacy of using classical LDH inhibitor oxamate and pembrolizumab alone or in combination in non-small cell lung cancer (NSCLC). We found that both oxamate and pembrolizumab monotherapy significantly delayed tumor growth; moreover, combination therapy showed better results. Immunofluorescence analysis showed that oxamate treatment increased the infiltration of activated CD8+ T cells in the tumor, which might have enhanced the therapeutic effects of pembrolizumab. Treatment of the humanized mice with anti-CD8 abrogated the therapeutic effects of oxamate, indicating CD8+ T cells as the main force mediating the effect of oxamate. In conclusion, Our preclinical findings position that oxamate not only inhibits tumor growth at a high safe dose but also enhances the efficacy of pembrolizumab in Hu-PBMC-CDX mice. Our study also provides a preclinical model for exploring the efficacy of other immune-based combination therapies for NSCLC.
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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 Socratic graph.