ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Suppression of Glut1 and Glucose Metabolism by Decreased Akt/mTORC1 Signaling Drives T Cell Impairment in B Cell Leukemia.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 151 citations in OpenAlex.
- Depletion of CLL cells by venetoclax treatment reverses oxidative stress and impaired glycolysis in CD4 T cells.Blood advances · 2022Trial
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Beyond PD-1/PD-L1: Reprogramming the Gynecologic Tumor Microenvironment by Targeting TIGIT and Myeloid Suppression.International journal of molecular sciences · 2026Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metabolic Adaptation of CD8⁺ T Cells Limits the Efficacy of Fatty Acid Oxidation Inhibition in Type 1 Diabetes.International journal of biological sciences · 2026Article
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- Ensemble quantitation of absolute metabolite concentrations in T cells reveals conserved features of immunometabolism.bioRxiv : the preprint server for biology · 2025Article
- Nutrient-gene therapy as a strategy to enhance CAR T cell function and overcome barriers in the tumor microenvironment.Journal of translational medicine · 2025Review
- Molecular mechanisms and clinical value of the correlation between depression and cancer.Medical oncology (Northwood, London, England) · 2025Review
- Interferon-driven Metabolic Reprogramming and Tumor Microenvironment Remodeling.Immune network · 2025Review
- Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy.Molecular cancer · 2025Review
- Fucoxanthin inhibits the proliferation of MOLM13 cells by targeting AKT to disrupt glucose metabolism.Frontiers in pharmacology · 2025Article
- PI3K-dependent reprogramming of hexokinase isoforms controls glucose metabolism and functional responses of B lymphocytes.iScience · 2024Article
- GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency.Nature communications · 2024Article
- Development of a Competitive Nutrient-Based T-Cell Immunotherapy Designed to Block the Adaptive Warburg Effect in Acute Myeloid Leukemia.Biomedicines · 2024Article
- Targeting metabolism to enhance immunotherapy within tumor microenvironment.Acta pharmacologica Sinica · 2024Review
- Ketone bodies rescue T cell impairments induced by low glucose availability.European journal of nutrition · 2024Article
- Deficiency of metabolic regulator PKM2 activates the pentose phosphate pathway and generates TCF1Nature immunology · 2024Article
- Growth Signaling Networks Orchestrate Cancer Metabolic Networks.Cold Spring Harbor perspectives in medicine · 2024Review
- T-cell dysfunction in CLL is mediated through expression of Siglec-10 ligands CD24 and CD52 on CLL cells.Blood advances · 2024Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Leukemia can promote T cell dysfunction and exhaustion that contributes to increased susceptibility to infection and mortality. The treatment-independent mechanisms that mediate leukemia-associated T cell impairments are poorly understood, but metabolism tightly regulates T cell function and may contribute. In this study, we show that B cell leukemia causes T cells to become activated and hyporesponsive with increased PD-1 and TIM3 expression similar to exhausted T cells and that T cells from leukemic hosts become metabolically impaired. Metabolic defects included reduced Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling, decreased expression of the glucose transporter Glut1 and hexokinase 2, and reduced glucose uptake. These metabolic changes correlated with increased regulatory T cell frequency and expression of PD-L1 and Gal-9 on both leukemic and stromal cells in the leukemic microenvironment. PD-1, however, was not sufficient to drive T cell impairment, as in vivo and in vitro anti-PD-1 blockade on its own only modestly improved T cell function. Importantly, impaired T cell metabolism directly contributed to dysfunction, as a rescue of T cell metabolism by genetically increasing Akt/mTORC1 signaling or expression of Glut1 partially restored T cell function. Enforced Akt/mTORC1 signaling also decreased expression of inhibitory receptors TIM3 and PD-1, as well as partially improved antileukemia immunity. Similar findings were obtained in T cells from patients with acute or chronic B cell leukemia, which were also metabolically exhausted and had defective Akt/mTORC1 signaling, reduced expression of Glut1 and hexokinase 2, and decreased glucose metabolism. Thus, B cell leukemia-induced inhibition of T cell Akt/mTORC1 signaling and glucose metabolism drives T cell dysfunction.
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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.