ArticleCell death & disease2024
Effects of methionine deficiency on B7H3-DAP12-CAR-T cells in the treatment of lung squamous cell carcinoma.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.Nature reviews. Cancer · 2026Review
- A novel microprotein L3EMP triggers lung adenocarcinoma progression by catalysing the deubiquitination of SIRT1.British journal of cancer · 2026Article
- Harnessing γδ T cells for B7-H3-targeting CAR therapy to enhance anti-tumor therapy in glioblastoma.Journal of translational medicine · 2026Article
- One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Harnessing the immune system: future directions in cancer immunotherapy.Frontiers in immunology · 2026Review
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- RNA Modifications in T cell Immunity: Mechanisms, Disease Relevance, and Therapeutic Potential.Theranostics · 2026Review
- Methionine restriction in cancer: a dietary insight for therapy.Frontiers in nutrition · 2026Review
- A Dual Role for NKG7 in T-cell Cytotoxicity and Longevity.Cancer immunology research · 2025Review
- Bi-directional metabolic reprogramming between cancer cells and T cells reshapes the anti-tumor immune response.PLoS biology · 2025Article
- Methionine Dependency and Restriction in Cancer: Exploring the Pathogenic Function and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Integrated multiomics machine learning and mediated Mendelian randomization investigate the molecular subtypes and prognosis lung squamous cell carcinoma.Translational lung cancer research · 2025Article
- Identification of immune-related prognostic biomarkers in lung squamous cell carcinoma microenvironment.Frontiers in immunology · 2025Article
- Leveraging innate immune signals in CD8+ T cells to boost antitumor immunity.Frontiers in immunology · 2025Review
- Applying metabolic control strategies to engineered T cell cancer therapies.Metabolic engineering · 2024Review
- Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.Journal of translational medicine · 2024Review
- CD8Frontiers in immunology · 2024Review
- Erianin promotes apoptosis and inhibits Akt-mediated aerobic glycolysis of cancer cells.Journal of Cancer · 2024Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer for which precision therapy is lacking. Chimeric antigen receptor T-cells (CAR-T) have the potential to eliminate cancer cells by targeting specific antigens. However, the tumor microenvironment (TME), characterized by abnormal metabolism could inhibit CAR-T function. Therefore, the aim of this study was to improve CAR-T efficacy in solid TME by investigating the effects of amino acid metabolism. We found that B7H3 was highly expressed in LUSC and developed DAP12-CAR-T targeting B7H3 based on our previous findings. When co-cultured with B7H3-overexpressing LUSC cells, B7H3-DAP12-CAR-T showed significant cell killing effects and released cytokines including IFN-γ and IL-2. However, LUSC cells consumed methionine (Met) in a competitive manner to induce a Met deficiency. CAR-T showed suppressed cell killing capacity, reduced cytokine release and less central memory T phenotype in medium with lower Met, while the exhaustion markers were up-regulated. Furthermore, the gene NKG7, responsible for T cell cytotoxicity, was downregulated in CAR-T cells at low Met concentration due to a decrease in m5C modification. NKG7 overexpression could partially restore the cytotoxicity of CAR-T in low Met. In addition, the anti-tumor efficacy of CAR-T was significantly enhanced when co-cultured with SLC7A5 knockdown LUSC cells at low Met concentration. In conclusion, B7H3 is a prospective target for LUSC, and B7H3-DAP12-CAR-T cells are promising for LUSC treatment. Maintaining Met levels in CAR-T may help overcome TME suppression and improve its clinical application potential.
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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.