ArticleBMC cancer2022
Restricting tumor lactic acid metabolism using dichloroacetate improves T cell functions.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
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- Metabolic Reprogramming in Oral Cancer: A Narrative Review of Therapeutic Perspectives with Emphasis on Dichloroacetate.Current issues in molecular biology · 2026Review
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- Hypoxia-Induced Ferroptosis Resistance Drives Orbital Fibrosis in Thyroid Eye Disease.Investigative ophthalmology & visual science · 2026Article
- Chemoresistance in the era of immunotherapy: challenges and novel combinatorial strategies for digestive system tumors.Frontiers in immunology · 2026Review
- Metabolic checkpoints in the regulation of Th17 cells: implications for uveitis pathogenesis and therapy.Frontiers in immunology · 2026Review
- The application of nanotechnology in regulating mitochondrial function in tumor microenvironment for cancer therapy.Theranostics · 2026Review
- Mitochondrial dysfunction as a metabolic checkpoint of immunotherapy response in colorectal cancer.Frontiers in immunology · 2026Review
- Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy.Journal of translational medicine · 2025Review
- C1QTNF1-AS1/miR-346 axis suppresses osteosarcoma progression via dual inhibition of LDHA/PDK1-mediated Warburg effect.BMC cancer · 2025Article
- Mechanisms of T-cell metabolic reprogramming in the microenvironment of acute myeloid leukemia and its therapeutic potential (Review).Oncology letters · 2025Review
- Sonodynamic biomimetic-nanomedicine fight cancers.Journal of nanobiotechnology · 2025Review
- Nutrient-gene therapy as a strategy to enhance CAR T cell function and overcome barriers in the tumor microenvironment.Journal of translational medicine · 2025Review
- Burning lactic acid: a road to revitalizing antitumor immunity.Frontiers of medicine · 2025Review
- Engineering immunity using metabolically active polymeric nanoparticles.Trends in biotechnology · 2025Review
- Reciprocal Modulation of Tumour and Immune Cell Motility: Uncovering Dynamic Interplays and Therapeutic Approaches.Cancers · 2025Review
- Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment.Cancer cell international · 2025Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLactic acid produced by tumors has been shown to overcome immune surveillance, by suppressing the activation and function of T cells in the tumor microenvironment. The strategies employed to impair tumor cell glycolysis could improve immunosurveillance and tumor growth regulation. Dichloroacetate (DCA) limits the tumor-derived lactic acid by altering the cancer cell metabolism. In this study, the effects of lactic acid on the activation and function of T cells, were analyzed by assessing T cell proliferation, cytokine production and the cellular redox state of T cells. We examined the redox system in T cells by analyzing the intracellular level of reactive oxygen species (ROS), superoxide and glutathione and gene expression of some proteins that have a role in the redox system. Then we co-cultured DCA-treated tumor cells with T cells to examine the effect of reduced tumor-derived lactic acid on proliferative response, cytokine secretion and viability of T cells.
resultWe found that lactic acid could dampen T cell function through suppression of T cell proliferation and cytokine production as well as restrain the redox system of T cells by decreasing the production of oxidant and antioxidant molecules. DCA decreased the concentration of tumor lactic acid by manipulating glucose metabolism in tumor cells. This led to increases in T cell proliferation and cytokine production and also rescued the T cells from apoptosis.
conclusionTaken together, our results suggest accumulation of lactic acid in the tumor microenvironment restricts T cell responses and could prevent the success of T cell therapy. DCA supports anti-tumor responses of T cells by metabolic reprogramming of tumor cells.
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