ArticleCellular & molecular immunology2024
CD8+ T cell metabolic flexibility elicited by CD28-ARS2 axis-driven alternative splicing of PKM supports antitumor immunity.
Article in Cellular & molecular immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.EBioMedicine · 2026Article
- Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models.Blood cancer discovery · 2026Article
- Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- A novel protein cPFKFB4 encoded by hsa_circ_0065394 strengthens PKM2-mediated glucose metabolic reprogramming to facilitate pancreatic cancer progression under hypoxia.Molecular cancer · 2025Article
- Pyruvate kinase M2 activation reprograms mitochondria in CD8 T cells, enhancing effector functions and efficacy of anti-PD1 therapy.Cell metabolism · 2025Article
- Integrating zinc homeostasis network and immune landscape: a five-gene prognostic framework for precision oncology in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Advances in CAR optimization strategies based on CD28.Frontiers in immunology · 2025Review
- Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma.Journal of translational medicine · 2024Article
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
- Endogenous CD28 drives CAR T cell responses in multiple myeloma.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2, a key determinant of CD8+ T-cell glucose utilization, interferon gamma production, and antitumor effector function. Importantly, PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation, revealing a novel means by which costimulation reprograms glucose metabolism in CD8+ T cells.
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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.