ArticleThe Journal of clinical investigation2024
Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it.
- LDH and glycolytic activity as predictors of immunotherapy response in gastric cancer: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- LDH isozymes as targets for cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 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 inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- The Dynamic Alliance of p53 and Metabolism in the Tumor Microenvironment Shapes Tumor Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Glucose Transporter 1 in Health and Disease.MedComm · 2026Review
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- Review
- Interplay between N6-methyladenosine RNA methylation and protein lactylation: a novel crosstalk linking metabolism and epigenetic regulation in human diseases.Journal of translational medicine · 2026Review
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Article
- Targeting the cancer metabolism-immunity interface: update and perspectives.Experimental hematology & oncology · 2026Review
- Beyond a waste product: lactate as a master metabolite dictating anti-tumor T-cell fate.Cell death & disease · 2026Review
- Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk.Acta pharmacologica Sinica · 2026Review
- T cell adaptation in chronic infections and tumors.Cellular & molecular immunology · 2026Review
- Locoregional lactate dehydrogenase inhibition potentiates therapy and overcomes treatment resistance in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2026Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Tumor reliance on glycolysis is a hallmark of cancer. Immunotherapy is more effective in controlling glycolysis-low tumors lacking lactate dehydrogenase (LDH) due to reduced tumor lactate efflux and enhanced glucose availability within the tumor microenvironment (TME). LDH inhibitors (LDHi) reduce glucose uptake and tumor growth in preclinical models, but their impact on tumor-infiltrating T cells is not fully elucidated. Tumor cells have higher basal LDH expression and glycolysis levels compared with infiltrating T cells, creating a therapeutic opportunity for tumor-specific targeting of glycolysis. We demonstrate that LDHi treatment (a) decreases tumor cell glucose uptake, expression of the glucose transporter GLUT1, and tumor cell proliferation while (b) increasing glucose uptake, GLUT1 expression, and proliferation of tumor-infiltrating T cells. Accordingly, increasing glucose availability in the microenvironment via LDH inhibition leads to improved tumor-killing T cell function and impaired Treg immunosuppressive activity in vitro. Moreover, combining LDH inhibition with immune checkpoint blockade therapy effectively controls murine melanoma and colon cancer progression by promoting effector T cell infiltration and activation while destabilizing Tregs. Our results establish LDH inhibition as an effective strategy for rebalancing glucose availability for T cells within the TME, which can enhance T cell function and antitumor immunity.
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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.