ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
FOXP3 expression diversifies the metabolic capacity and enhances the efficacy of CD8 T cells in adoptive immunotherapy of melanoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Regulatory T cell therapies: biological foundations, engineering strategies, and clinical translation.Frontiers in immunology · 2026Review
- Novel Predictive Spatial Biomarker in Non-Small Cell Lung Carcinoma: The Diversity of Niches Unlocking Treatment Sensitivity (DONUTS).bioRxiv : the preprint server for biology · 2025Article
- Regulatory T cells in cancer anti-PD-(L)1 therapy.Human cell · 2025Review
- Immunometabolism of regulatory T cells in cancer.Oncogene · 2025Review
- Nutrition and Diet Patterns as Key Modulators of Metabolic Reprogramming in Melanoma Immunotherapy.Journal of clinical medicine · 2025Review
- Review
- The immune landscape of the inflamed joint defined by spectral flow cytometry.Clinical and experimental immunology · 2024Article
- Lipid metabolism in tumor-infiltrating regulatory T cells: perspective to precision immunotherapy.Biomarker research · 2024Review
- IFI27 enhances bladder cancer immunotherapy response by modulating regulatory T cell enrichment.Journal of Cancer · 2024Article
- Glycolysis in the tumor microenvironment: a driver of cancer progression and a promising therapeutic target.Frontiers in cell and developmental biology · 2024Review
- Specific Polo-Like Kinase 1 Expression in Nodular Lymphocyte-Predominant Hodgkin Lymphoma Suggests an Intact Immune Surveillance Program.The American journal of pathology · 2024Article
- Effects of altered glycolysis levels on CD8Cell death & disease · 2023Review
- Lipid metabolism in tumor-infiltrating T cells: mechanisms and applications.Life metabolism · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T cells overwhelm conventional T cells in the tumor microenvironment (TME) thanks to a FOXP3-driven metabolic program that allows them to engage different metabolic pathways. Using a melanoma model of adoptive T cell therapy (ACT), we show that FOXP3 overexpression in mature CD8 T cells improved their antitumor efficacy, favoring their tumor recruitment, proliferation, and cytotoxicity. FOXP3-overexpressing (Foxp3UP) CD8 T cells exhibited features of tissue-resident memory-like and effector T cells, but not suppressor activity. Transcriptomic analysis of tumor-infiltrating Foxp3UP CD8 T cells showed positive enrichment in a wide variety of metabolic pathways, such as glycolysis, fatty acid (FA) metabolism, and oxidative phosphorylation (OXPHOS). Intratumoral Foxp3UP CD8 T cells exhibited an enhanced capacity for glucose and FA uptake as well as accumulation of intracellular lipids. Interestingly, Foxp3UP CD8 T cells compensated for the loss of mitochondrial respiration-driven ATP production by activating aerobic glycolysis. Moreover, in limiting nutrient conditions these cells engaged FA oxidation to drive OXPHOS for their energy demands. Importantly, their ability to couple glycolysis and OXPHOS allowed them to sustain proliferation under glucose restriction. Our findings demonstrate a hitherto unknown role for FOXP3 in the adaptation of CD8 T cells to TME that may enhance their efficacy in ACT.
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