ArticleThe Journal of clinical investigation2016
Glycolysis determines dichotomous regulation of T cell subsets in hypoxia.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 107 citations in OpenAlex.
- Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals.The Journal of clinical investigation · 2020Trial
- Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-invasive Imaging Application.Cancer research and treatment · 2026Review
- Epigenetic and transcriptomic analysis revealed ceRNA regulatory network in glioblastoma multiforme.European journal of medical research · 2025Article
- Single-cell RNA sequencing reveals different cellular states in malignant cells and the tumor microenvironment in primary and metastatic ER-positive breast cancer.NPJ breast cancer · 2025Article
- MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH.Cellular & molecular immunology · 2025Article
- The General Principle of the Warburg Effect as a Possible Approach for Cancer Immunotherapy: The Regulatory Effect of Plant Extracts Could Change the Game.Molecules (Basel, Switzerland) · 2025Review
- Harnessing CD8Clinical and translational medicine · 2024Review
- Analysis and Interpretation of Automated Blood Count in the Treatment of Chronic Paracoccidioidomycosis.Journal of fungi (Basel, Switzerland) · 2024Article
- Single-cell analysis of the CD8Haematologica · 2024Article
- Unlocking the potential of T-cell metabolism reprogramming: Advancing single-cell approaches for precision immunotherapy in tumour immunity.Clinical and translational medicine · 2024Review
- Regulation of CD8Cellular & molecular immunology · 2023Review
- T cell metabolic reprogramming in acute kidney injury and protection by glutamine blockade.JCI insight · 2023Article
- Oxygen levels at the time of activation determine T cell persistence and immunotherapeutic efficacy.eLife · 2023Article
- Memory CD8European journal of immunology · 2023Article
- Review
- Review
- The mutual interaction of glycolytic enzymes and RNA in post-transcriptional regulation.RNA (New York, N.Y.) · 2022Review
- Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer.Nature communications · 2022Article
- Cancer cell autophagy, reprogrammed macrophages, and remodeled vasculature in glioblastoma triggers tumor immunity.Cancer cell · 2022Article
- Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells.Nature biotechnology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypoxia occurs in many pathological conditions, including chronic inflammation and tumors, and is considered to be an inhibitor of T cell function. However, robust T cell responses occur at many hypoxic inflammatory sites, suggesting that functions of some subsets are stimulated under low oxygen conditions. Here, we investigated how hypoxic conditions influence human T cell functions and found that, in contrast to naive and central memory T cells (TN and TCM), hypoxia enhances the proliferation, viability, and cytotoxic action of effector memory T cells (TEM). Enhanced TEM expansion in hypoxia corresponded to high hypoxia-inducible factor 1α (HIF1α) expression and glycolytic activity compared with that observed in TN and TCM. We determined that the glycolytic enzyme GAPDH negatively regulates HIF1A expression by binding to adenylate-uridylate-rich elements in the 3'-UTR region of HIF1A mRNA in glycolytically inactive TN and TCM. Conversely, active glycolysis with decreased GAPDH availability in TEM resulted in elevated HIF1α expression. Furthermore, GAPDH overexpression reduced HIF1α expression and impaired proliferation and survival of T cells in hypoxia, indicating that high glycolytic metabolism drives increases in HIF1α to enhance TEM function during hypoxia. This work demonstrates that glycolytic metabolism regulates the translation of HIF1A to determine T cell responses to hypoxia and implicates GAPDH as a potential mechanism for controlling T cell function in peripheral tissue.
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What OpenQuestion holds
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.