ArticleSignal transduction and targeted therapy2025
Oleic acid restores the impaired antitumor immunity of γδ-T cells induced by palmitic acid.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- Ex vivo pretreatment with venetoclax boosts antileukemic efficacy of therapeutic γδ T cells in AML models.The Journal of clinical investigation · 2026Article
- Genome editing generates high oleic soybean and eliminates beany flavors.Journal of integrative plant biology · 2026Article
- Synthesis of Cyclopropene-Modified Fatty Acids Allows Single-Cell Quantification of Uptake by Immune Cells.Angewandte Chemie (International ed. in English) · 2026Article
- Tumor-derived stearic acid induces macrophage Egr2 signaling to suppress anti-tumor immunity in breast cancer.bioRxiv : the preprint server for biology · 2026Article
- High-fat diet leads to male reproductive dysfunction by disrupting lipid-droplet-mediated organelle crosstalk.Cellular & molecular biology letters · 2026Article
- Nutritional modulation of metabolic signaling within the tumor microenvironment for cancer therapy.Molecular and cellular biochemistry · 2026Review
- Programmed cell death inhibitors: a new hope for cancer therapy?World journal of surgical oncology · 2026Review
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- High Ratio of Dietary Palmitic Acid to DHA + EPA Induces Glucose Metabolic Disorder Through Endocrine and Transcriptional Regulation in Large Yellow Croaker (Metabolites · 2026Article
- Acyl-CoA thioesterases and their derived lipid mediators: linking Acyl-CoA metabolic reprogramming to the tumor microenvironment.Frontiers in immunology · 2026Review
- Repurposing dimethyl fumarate for cancer therapy: current evidence and future directions.Frontiers in pharmacology · 2025Review
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Authors and funding
21 authors.
Funding
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Abstract
Dietary fatty acids (FAs) are associated with the therapeutic intervention under various health conditions. Human γδ-T cells are indispensable for immunosurveillance toward malignant cells. However, their impact on γδ-T cell metabolism and function remains poorly unexplored. Here, we applied targeted metabolomics analysis to serum FAs among cancer patients undergoing γδ-T cell therapy and discovered that palmitic acid (PA) or oleic acid (OA) levels were associated with the efficacy of Vγ9Vδ2-T cell therapy. We further elucidated that PA suppresses the antitumor activity of Vγ9Vδ2-T cells by disrupting metabolic processes and inhibiting the secretion of lytic granules, whereas OA restores the impaired antitumor activity of Vγ9Vδ2-T cells. Mechanistically, we surprisingly found that PA stimulates Vγ9Vδ2-T cells to secrete excessive IFNγ, which in turn induces cell pyroptosis, ultimately resulting in decreased antitumor activity. In contrast, OA reduces IFNγ secretion and mitigates cell pyroptosis, thereby restoring their antitumor activity. Alternatively, direct blockade of IFNγ by anti-IFNγ mAb or inhibition of pyroptosis by dimethyl fumarate (DMF) also restores their antitumor activity. This study highlights a novel mechanism whereby dietary FAs modulate γδ-T cell function through regulating IFNγ-mediated pyroptosis. Additionally, it offers proof-of-concept for an innovative approach by targeting IFNγ-mediated pyroptosis or dietary OA supplementation to strengthen the antitumor immunity of γδ-T cells against cancers.
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