ArticleCells2022
Unbalanced Glutamine Partitioning between CD8T Cells and Cancer Cells Accompanied by Immune Cell Dysfunction in Hepatocellular Carcinoma.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Single-cell profiling reveals peripheral blood immune landscape remodelling in breast cancer lymph node metastasis.Clinical and translational medicine · 2026Article
- Overview of glutamine metabolism in stromal components of the tumor microenvironment and potential anti-tumor therapies.Genes & diseases · 2026Review
- Integrative machine learning models reveal immune and metabolic signatures predictive of colorectal cancer prognosis.Discover oncology · 2026Article
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Decoding the cholesterol-apoptosis axis in HCC: a machine learning-based multi-omics integration and single-cell transcriptomic analysis.Discover oncology · 2025Article
- Pan-cancer analysis of HOMER1 in hepatocellular carcinoma revealing diagnostic potential and immune landscape with experimental validation.Discover oncology · 2025Article
- Genetic evidence for the causal influence of inflammatory factors on intrahepatic cholangiocarcinoma risk.World journal of gastrointestinal oncology · 2025Article
- Targeting glutamine metabolism as a potential target for cancer treatment.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting tumor metabolism to augment CD8Journal of pharmaceutical analysis · 2025Review
- The impact of metabolic reprogramming on tertiary lymphoid structure formation: enhancing cancer immunotherapy.BMC medicine · 2025Review
- New insights into T cell metabolism in liver cancer: from mechanism to therapy.Cell death discovery · 2025Review
- Glutamine's double-edged sword: fueling tumor growth and offering therapeutic hope.Frontiers in immunology · 2025Review
- Comprehensive pan-cancer analysis identifies PLAG1 as a key regulator of tumor immune microenvironment and prognostic biomarker.Frontiers in immunology · 2025Article
- Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.Frontiers in immunology · 2025Review
- Harnessing CD8Clinical and translational medicine · 2024Review
- The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Glutamine metabolism, a double agent combating or fuelling hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2024Review
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
- Metabolic reprogramming in the tumor microenvironment of liver cancer.Journal of hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Glutamine metabolism is critical both for the proliferation of cancer cells and the activation of CD8T cells to kill cancer cells. We aim to explore the relationship between the glutamine metabolism of CD8T cells and cancer cells and tumor immunity in the tumor microenvironment. In a TCGA cohort, we found that patients with high scores of glutamine-metabolism-related genes showed poor prognoses, and that a high score of glutamine-metabolism-related genes was an independent risk factor for HCC patients. In single-cell RNA-seq data, we found that, in some patients, the glutamine metabolism gene scores of tumor cells were significantly higher than those of CD8T cells, while decreased ratios of CD8-Tef-GZMA and suppressed tumor-killing activity of CD8-Tef-APOC2 were observed. A further genetic dynamics pseudotime analysis suggested that immune remodeling of these two subpopulations was accompanied by metabolic reprogramming. CD8-Tef-APOC2 in the dominant group tended to metabolize exogenous lipids, while the metabolic program of CD8-Tef-GZMA in the nondominant group was characterized by amino acid and endogenous lipid synthesis. In addition, we found that the glutamine metabolism inhibitor JHU083 promoted the proliferation of CD8T cells and improved the efficacy of PD-1 blockers. We proposed a new tool to quantify the glutamine partitioning between tumor cells and CD8T cells, through which the unique immune microenvironment could be identified at the transcriptome level. Furthermore, the simultaneous destruction of the glutamine metabolism in tumor cells and CD8T cells facilitated the enrichment of tumor-infiltrating CD8T cells and enhanced the efficacy of immunotherapy.
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Registered trials
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