ArticleJCI insight2020
CD28 costimulation drives tumor-infiltrating T cell glycolysis to promote inflammation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
69 citing papers in PubMed, 88 citations in OpenAlex.
- Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.Nature reviews. Cancer · 2026Review
- The Glucose Transporter GLUT3 Controls Regulatory T Cell Function.European journal of immunology · 2026Article
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- ICAM-1 promotes T cell glycolytic reprogramming and tumor infiltration to drive 18F-FDG PET flares following radiotherapy.Protein & cell · 2026Article
- Mitochondrial transfer between tumor and immune cells: a nexus of metabolic adaptation and immune dysfunction.Biomarker research · 2026Review
- Mitochondrial potential reflects T cell fitness and function during cancer immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Metabolic vulnerabilities and therapeutic opportunities in diffuse large B-cell lymphoma.Oncogenesis · 2026Review
- Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models.Blood cancer discovery · 2026Article
- Pharmacologic DPP-4 inhibition promotes CD8bioRxiv : the preprint server for biology · 2026Article
- Integrating T cell signaling and metabolism to enhance T cell engager responses in solid tumors.Frontiers in immunology · 2026Review
- Loss ofLife science alliance · 2026Article
- METTL14 MediatesRedox report : communications in free radical research · 2025Article
- CD28 and ICOS in immune regulation: Structural insights and therapeutic targeting.Bioorganic & medicinal chemistry letters · 2025Review
- Diet-induced dyslipidemia enhances IFN-γ production in mycolic acid-specific T cells and affects mycobacterial control.Mucosal immunology · 2025Article
- Mitochondrial Regulation of CD8⁺ T Cells: Mechanisms and Therapeutic Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Reciprocal Modulation of Tumour and Immune Cell Motility: Uncovering Dynamic Interplays and Therapeutic Approaches.Cancers · 2025Review
- Glut3 overexpression improves environmental glucose uptake and antitumor efficacy of CAR-T cells in solid tumors.Journal for immunotherapy of cancer · 2025Article
- Review
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Metabolic reprogramming dictates the fate and function of stimulated T cells, yet these pathways can be suppressed in T cells in tumor microenvironments. We previously showed that glycolytic and mitochondrial adaptations directly contribute to reducing the effector function of renal cell carcinoma (RCC) CD8+ tumor-infiltrating lymphocytes (TILs). Here we define the role of these metabolic pathways in the activation and effector functions of CD8+ RCC TILs. CD28 costimulation plays a key role in augmenting T cell activation and metabolism, and is antagonized by the inhibitory and checkpoint immunotherapy receptors CTLA4 and PD-1. While RCC CD8+ TILs were activated at a low level when stimulated through the T cell receptor alone, addition of CD28 costimulation greatly enhanced activation, function, and proliferation. CD28 costimulation reprogrammed RCC CD8+ TIL metabolism with increased glycolysis and mitochondrial oxidative metabolism, possibly through upregulation of GLUT3. Mitochondria also fused to a greater degree, with higher membrane potential and overall mass. These phenotypes were dependent on glucose metabolism, as the glycolytic inhibitor 2-deoxyglucose both prevented changes to mitochondria and suppressed RCC CD8+ TIL activation and function. These data show that CD28 costimulation can restore RCC CD8+ TIL metabolism and function through rescue of T cell glycolysis that supports mitochondrial mass and activity.
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Registered trials
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.