ArticleOncogene2026
LDHA-driven lactate metabolism promotes MDSC activation and immunosuppressive microenvironment in prostate cancer.
Article in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Neutrophil-driven immunosuppression in cancer.Cell insight · 2026Review
- Myeloid-derived suppressor cells in cancer: biology, regulatory networks and theranostic prospects.Signal transduction and targeted therapy · 2026Review
- Metabolic convergence of diabetes and prostate cancer: from dysglycemia to tumor microenvironment reprogramming.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- Myeloid-Derived Suppressor Cells in Cancer: Metabolic Reprogramming, Immune Crosstalk, and Therapeutic Targeting.Cancers · 2026Review
- Metabolic-epigenetic crosstalk in latent autoimmune diabetes in adults: potential roles of lactate-induced histone lactylation in immune regulation and pancreatic β-cell fate.Frontiers in endocrinology · 2026Review
- The lactylation axis: bridging metabolic reprogramming and immunosuppression in the tumor microenvironment.Frontiers in immunology · 2026Review
- ANP32A interacts with LDHA to modulate glycolysis and ferroptosis in hepatocellular carcinoma.Frontiers in oncology · 2026Article
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapy has achieved limited efficacy in prostate cancer (PCa), largely due to its profoundly immunosuppressive tumor microenvironment (TME). However, the metabolic mechanisms underpinning this immune resistance remain poorly defined. Here, we identify lactate dehydrogenase A (LDHA)-driven lactate metabolism as a critical regulator of myeloid-derived suppressor cell (MDSC) activation in PCa. Integrated metabolomic, single-cell, and spatial transcriptomic analyses revealed that LDHA is highly expressed in PCa malignant epithelial cells and correlates with increased lactate production and immune exclusion. LDHA-high tumors exhibited enriched infiltration of polymorphonuclear MDSCs (PMN-MDSCs), which were spatially co-localized with LDHA-positive tumor regions. Mechanistically, lactate uptake through monocarboxylate transporter 1 (MCT1) enhanced PMN-MDSC differentiation and upregulated Arg1 and NOS2, reinforcing T cell suppression. Genetic ablation of LDHA in murine models markedly reduced PMN-MDSC infiltration, restored CD8
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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.