ArticleThe Journal of clinical investigation2022
IL-9/STAT3/fatty acid oxidation-mediated lipid peroxidation contributes to Tc9 cell longevity and enhanced antitumor activity.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 91 citations in OpenAlex.
- Host metadherin coordinates hepatic lipid metabolism and CD8Cell metabolism · 2026Article
- Upadacitinib Restrains the Pathogenic Fitness of CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bap1-mediated deubiquitination determines immune tolerance and anti-tumor immunity via modulating eTreg cell differentiation and ferroptosis.Cell death and differentiation · 2026Article
- Ferroptosis in T cells: mechanisms, biology and translational opportunities.Nature reviews. Immunology · 2026Review
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- GPX4 in the Tumor Microenvironment: Not Just Inhibiting Ferroptosis, but Immuno-Metabolic Regulation.Biomolecules · 2026Review
- Multifunctional Role of Mitochondrial Fatty Acid Oxidation in Cancer Immunotherapy and Aging.Cancer science · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Extracellular ATP Functions as a Metabolic Lineage Selection Signal That Stabilizes Tc9 Cells During Adoptive T Cell Therapy.International journal of molecular sciences · 2026Article
- Fatty acid oxidation drives acetyl-CoA-dependent H3K9ac reprogramming to promote adaptive resistance to BRAFCell death & disease · 2026Article
- Cysteine addiction in drug resistant glioblastoma and therapeutic targeting with designer selenium compounds.Neuro-oncology · 2026Article
- Targeting metabolic reprogramming to enhance adoptive immunotherapy: emerging mechanisms and translational perspectives.Journal of translational medicine · 2026Review
- Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions.World journal of clinical oncology · 2026Review
- Active aldehydes accelerate CD8Nature immunology · 2026Article
- Potential crosstalk between ferroptosis and immunosenescence in osteoarthritis: evidence integration and translational insights from the osteoimmune microenvironment.Frontiers in immunology · 2026Review
- Ferroptosis reshapes the tumor immune microenvironment: molecular mechanisms, immune regulation, and therapeutic synergistic strategies.Frontiers in immunology · 2026Review
- Targeted protein degradation: species, diseases and efficient utilization.Journal of translational medicine · 2025Review
- Advanced glycation end products exacerbate lipopolysaccharide-induced acute lung injury with diabetes by promoting ferroptosis via AMP-activated protein kinase/acetyl-CoA carboxylase signaling.Scientific reports · 2025Article
- Immune cells dying from ferroptosis: mechanisms and therapeutic opportunities.Cell death & disease · 2025Review
- Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
Abstract
CD8+ T cell longevity regulated by metabolic activity plays important roles in cancer immunotherapy. Although in vitro-polarized, transferred IL-9-secreting CD8+ Tc9 (cytotoxic T lymphocyte subset 9) cells exert greater persistence and antitumor efficacy than Tc1 cells, the underlying mechanism remains unclear. Here, we show that tumor-infiltrating Tc9 cells display significantly lower lipid peroxidation than Tc1 cells in several mouse models, which is strongly correlated with their persistence. Using RNA-sequence and functional validation, we found that Tc9 cells exhibited unique lipid metabolic programs. Tc9 cell-derived IL-9 activated STAT3, upregulated fatty acid oxidation and mitochondrial activity, and rendered Tc9 cells with reduced lipid peroxidation and resistance to tumor- or ROS-induced ferroptosis in the tumor microenvironment. IL-9 signaling deficiency, inhibiting STAT3, or fatty acid oxidation increased lipid peroxidation and ferroptosis of Tc9 cells, resulting in impaired longevity and antitumor ability. Similarly, human Tc9 cells also exhibited lower lipid peroxidation than Tc1 cells and tumor-infiltrating CD8+ T cells expressed lower IL9 and higher lipid peroxidation- and ferroptosis-related genes than circulating CD8+ T cells in patients with melanoma. This study indicates that lipid peroxidation regulates Tc9 cell longevity and antitumor effects via the IL-9/STAT3/fatty acid oxidation pathway and regulating T cell lipid peroxidation can be used to enhance T cell-based immunotherapy in human cancer.
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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.