ArticleCancer immunology research2023
Ncoa2 Promotes CD8+ T cell-Mediated Antitumor Immunity by Stimulating T-cell Activation via Upregulation of PGC-1α Critical for Mitochondrial Function.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- On the Edge of Benefit and Harm: Reactive Oxygen Species in Cancer.International journal of molecular sciences · 2026Review
- Unveiling medication patterns in traditional Chinese medicine for the prevention of colorectal cancer recurrence: from potential combinations to validation of components and targets.Chinese medicine · 2026Article
- Roles of mitophagy and immune infiltration in Parkinson's disease: new perspectives from bioinformatics analysis and A53T transgenic mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- NCOA2 promotes the return of hematopoietic stem cells to quiescence after irradiation stress by regulating FOXO3a-dependent mitophagy.HemaSphere · 2026Article
- Mitochondria: from powerhouses of cells to hubs in antitumor immunity.Frontiers in immunology · 2026Review
- Development and validation of a radiogenomics prognostic model integrating PET/CT radiomics and glucose metabolism-related gene signatures for non-small cell lung cancer.European journal of nuclear medicine and molecular imaging · 2025Article
- Mitochondrial Regulation of CD8⁺ T Cells: Mechanisms and Therapeutic Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Article
- Mitochondrial function changes in T cell subsets during radiotherapy for patients with nasopharyngeal carcinoma.Oncology letters · 2025Article
- Monocyte/macrophage-derived IL-15 activates STAT5 to trigger the EFNA1/NCOA2-positive feedback loop, facilitating retinal angiogenesis in high-glucose environments.Molecular vision · 2025Article
- Tumor microenvironment-driven resistance to immunotherapy in non-small cell lung cancer: strategies for Cold-to-Hot tumor transformation.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Enhancing CAR-T Cell Metabolic Fitness and Memory Phenotype for Improved Efficacy against Hepatocellular Carcinoma.International journal of biological sciences · 2025Article
- Fueling CARs: metabolic strategies to enhance CAR T-cell therapy.Experimental hematology & oncology · 2024Review
- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- Population Structure and Selection Signal Analysis of Nanyang Cattle Based on Whole-Genome Sequencing Data.Genes · 2024Review
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Impact of mitochondrial dysfunction on the antitumor effects of immune cells.Frontiers in immunology · 2024Review
- Function of Steroid Receptor Coactivators in T Cells and Cancers: Implications for Cancer Immunotherapy.Critical reviews in immunology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Nuclear receptor coactivator 2 (Ncoa2) is a member of the Ncoa family of coactivators, and we previously showed that Ncoa2 regulates the differentiation of induced regulatory T cells. However, it remains unknown if Ncoa2 plays a role in CD8+ T-cell function. Here, we show that Ncoa2 promotes CD8+ T cell-mediated immune responses against tumors by stimulating T-cell activation via upregulating PGC-1α expression to enhance mitochondrial function. Mice deficient in Ncoa2 in T cells (Ncoa2fl/fl/CD4Cre) displayed defective immune responses against implanted MC38 tumors, which associated with significantly reduced tumor-infiltrating CD8+ T cells and decreased IFNγ production. Consistently, CD8+ T cells from Ncoa2fl/fl/CD4Cre mice failed to reject tumors after adoptive transfer into Rag1-/- mice. Further, in response to TCR stimulation, Ncoa2fl/fl/CD4Cre CD8+ T cells failed to increase mitochondrial mass, showed impaired oxidative phosphorylation, and had lower expression of PGC-1α, a master regulator of mitochondrial biogenesis and function. Mechanically, T-cell activation-induced phosphorylation of CREB triggered the recruitment of Ncoa2 to bind to enhancers, thus, stimulating PGC-1α expression. Forced expression of PGC-1α in Ncoa2fl/fl/CD4Cre CD8+ T cells restored mitochondrial function, T-cell activation, IFNγ production, and antitumor immunity. This work informs the development of Ncoa2-based therapies that modulate CD8+ T cell-mediated antitumor immune responses.
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