ArticleCancer research2022
Intracellular Acetyl CoA Potentiates the Therapeutic Efficacy of Antitumor CD8+ T Cells.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Post-Translational Regulation of CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- miR-4652-3p suppresses glutamine metabolism induced by the inflammatory microenvironment in non-small cell lung cancer by regulating MYC/SLC1A5.Hereditas · 2026Article
- Metabolomics Reveals Potential Biomarkers for Early Detection of irAEs in ICI-Treated Patients.Drug design, development and therapy · 2026Article
- Metabolic Checkpoints in CD8International journal of biological sciences · 2026Review
- Article
- Sucrose supplementation mitigates heat stress-induced alterations in rumen metabolism and immunity in dairy cows.Scientific reports · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- Cytokine-mediated regulation of immune cell metabolic pathways in the tumor microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.Molecular cancer · 2025Review
- Innovative approaches to CAR-T cell therapy: the role of lipid metabolism pathways.Journal of translational medicine · 2025Review
- Genetic insights support PARP1 as a mediator in the protective association of ATP-citrate lyase inhibitors with melanoma.Communications biology · 2025Article
- A feedforward loop between ACLY and MYC supports T-ALL progression in vivo.Blood neoplasia · 2025Article
- Targeting tumor metabolism to augment CD8Journal of pharmaceutical analysis · 2025Review
- Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications.Molecular cancer · 2025Review
- Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies.Cell death & disease · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Effector CD8+ T cells rely primarily on glucose metabolism to meet their biosynthetic and functional needs. However, nutritional limitations in the tumor microenvironment can cause T-cell hyporesponsiveness. Therefore, T cells must acquire metabolic traits enabling sustained effector function at the tumor site to elicit a robust antitumor immune response. Here, we report that IL12-stimulated CD8+ T cells have elevated intracellular acetyl CoA levels and can maintain IFNγ levels in nutrient-deprived, tumor-conditioned media (TCM). Pharmacological and metabolic analyses demonstrated an active glucose-citrate-acetyl CoA circuit in IL12-stimulated CD8+ T cells supporting an intracellular pool of acetyl CoA in an ATP-citrate lyase (ACLY)-dependent manner. Intracellular acetyl CoA levels enhanced histone acetylation, lipid synthesis, and IFNγ production, improving the metabolic and functional fitness of CD8+ T cells in tumors. Pharmacological inhibition or genetic knockdown of ACLY severely impaired IFNγ production and viability of CD8+ T cells in nutrient-restricted conditions. Furthermore, CD8+ T cells cultured in high pyruvate-containing media in vitro acquired critical metabolic features of IL12-stimulated CD8+ T cells and displayed improved antitumor potential upon adoptive transfer in murine lymphoma and melanoma models. Overall, this study delineates the metabolic configuration of CD8+ T cells required for stable effector function in tumors and presents an affordable approach to promote the efficacy of CD8+ T cells for adoptive T-cell therapy. SIGNIFICANCE: IL12-mediated metabolic reprogramming increases intracellular acetyl CoA to promote the effector function of CD8+ T cells in nutrient-depleted tumor microenvironments, revealing strategies to potentiate the antitumor efficacy of T cells.
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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.