ArticleCell metabolism2018
Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death.
Article in Cell metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
- Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning.International journal of hematology · 2020Trial
- Exploiting vitamin C as a prooxidant to activate ROS-responsive prodrugs for potent and selective tumor killing.Redox biology · 2026Article
- Serum Antioxidant Capacity Predicts Prognosis in Patients with Metastatic Colorectal Cancer: An Original Cohort Study.Antioxidants (Basel, Switzerland) · 2026Article
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- Exploration of oxidative stress-related molecular signature for clear cell renal cell carcinoma.Discover oncology · 2025Article
- Machine learning-based screening and validation of liver metastasis-specific genes in colorectal cancer.Scientific reports · 2024Article
- Pan-cancer analysis of T-cell proliferation regulatory genes as potential immunotherapeutic targets.Aging · 2024Article
- Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling.Biomolecules · 2024Review
- Modulating ferroptosis sensitivity: environmental and cellular targets within the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2024Review
- Acute remote ischemic conditioning enhances (CD3+)- but not (FoxP3+)-T-cell invasion in the tumor center and increases IL 17 and TNF-alpha expression in a murine melanoma model.Frontiers in immunology · 2024Article
- Impact and potential value of immunosenescence on solid gastrointestinal tumors.Frontiers in immunology · 2024Review
- Imaging and AI based chromatin biomarkers for diagnosis and therapy evaluation from liquid biopsies.NPJ precision oncology · 2023Article
- Investigating subtypes of lung adenocarcinoma by oxidative stress and immunotherapy related genes.Scientific reports · 2023Article
- Regulation of Tumor Apoptosis ofNutrients · 2023Article
- Development and Validation of the Oxidative Stress Related lncRNAs for Prognosis in Esophageal Squamous Cell Carcinoma.Cancers · 2023Article
- MTA1, a Novel ATP Synthase Complex Modulator, Enhances Colon Cancer Liver Metastasis by Driving Mitochondrial Metabolism Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Neutrophil-intrinsic TNF receptor signaling orchestrates host defense againstScience advances · 2023Article
- Methionine consumption by cancer cells drives a progressive upregulation of PD-1 expression in CD4 T cells.Nature communications · 2023Article
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Ginseng polysaccharides: Potential antitumor agents.Journal of ginseng research · 2023Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The inhibitory effects of cancer on T cell metabolism have been well established, but the metabolic impact of immunotherapy on tumor cells is poorly understood. Here, we developed a CD4+ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, we show that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species (ROS) in tumor cells. We further demonstrate that T cell-derived tumor necrosis factor alpha (TNF-α) can synergize with chemotherapy to intensify oxidative stress and tumor cell death in an NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase-dependent manner. Reduction of oxidative stress, by preventing TNF-α-signaling in tumor cells or scavenging ROS, antagonized the therapeutic effects of adoptive immunotherapy. Conversely, provision of pro-oxidants after chemotherapy can partially recapitulate the antitumor effects of T cell transfer. These findings imply that reinforcing tumor oxidative stress represents an important mechanism underlying the efficacy of adoptive immunotherapy.
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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.