ArticleCell communication and signaling : CCS2025
Intrinsic STING of CD8 + T cells regulates self-metabolic reprogramming and memory to exert anti-tumor effects.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Prognostic Value of Perioperative Inflammatory-Immune-Nutritional Indicators in Advanced Gallbladder Cancer.Cancer medicine · 2026Article
- TRIM32-mediated ubiquitination of STING promotes glycolysis and tumor progression.Cell death and differentiation · 2026Article
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Advances in miRNA-Mediated Bidirectional Crosstalk and Immune Evasion Mechanisms Between Lung Cancer Cells and CD8International journal of molecular sciences · 2026Review
- Biomimetic self-assembled copper nanoadjuvant potentiates hepatocellular carcinoma immunotherapy via cuproptosis-driven cGAS-STING activation.Materials today. Bio · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- p300-mediated histone H3K18 lactylation promotes mitochondrial ROS accumulation via mitophagy inhibition to potentiate dopamine agonists efficacy in prolactinomas.Redox biology · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Targeting DNA Damage Response and Immune Crosstalk in Cancer: Mechanistic Insights and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
- Immunometabolic reprogramming in lung cancer: interplay between immune and stem-like cells in immune checkpoint inhibitor resistance.Journal of translational medicine · 2025Review
- Neurodegeneration rewires the tumor microenvironment via the neuro-immune-cancer axis.iScience · 2025Review
- MiR-4664-3p as a potential diagnostic, prognostic, and immunotherapeutic biomarker in NSCLC: modulation of tumor progression through CD8 + T cell regulation.Frontiers in oncology · 2025Article
- Immunogenic cell death genes in single-cell and transcriptome analyses perspectives from a prognostic model of cervical cancer.Frontiers in genetics · 2025Article
- Hexokinase 2 promotes tumor development and progression.American journal of cancer research · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
backgroundOur team has previously found that the stimulator of interferon genes (STING) plays a more significant anti-tumor role in host immune cells than in tumor cells. Although STING is necessary for CD8 + T cells to exert immunological activity, its effect on CD8 + T cells remains debatable. In this study, we used both in vitro and in vivo models to explore the metabolic effects of STING on CD8 + T cells.
methodsPeripheral blood lymphocytes were procured from non-small cell lung cancer (NSCLC) patients receiving anti-PD-1 therapy to investigate the correlation between STING expression levels, CD8 + T-cell subsets, and immunotherapy efficacy. STING knockout (STING-KO) mice were used for in vivo studies. RNA-seq, seahorse, flow cytometry, electron microscopy, qPCR, immunofluorescence, western blotting, and immunoprecipitation were performed to explore the underlying mechanisms of STING in regulating CD8 + T cell function.
resultsWe discovered that the expression level of STING in immune cells exhibited a significant correlation with immunotherapy efficacy, as well as with the proportion of central memory CD8 + T cells. Moreover, we found that the loss of the STING gene results in a reduction in the number of mitochondria and a change in the metabolic pathway selection, thereby inducing excessive glycolysis in CD8 + T cells. This excessive glycolysis generates high levels of lactate, which further inhibits IFN-γ secretion and impacts memory T cell differentiation. Correcting the glycolysis disorder partially restored function and IFN-γ secretion, rescued the central memory CD8 + T subset, and improved immunotherapy in STING-KO mice. This provides a new treatment strategy for patients with low STING expression and a poor response to immunotherapy.
conclusionIntrinsic STING of CD8 + T cells affects their function through the HK2/Lactate/IFN-γ axis and affects memory differentiation by regulating glycolysis.
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