ArticleJournal of experimental & clinical cancer research : CR2022
Mitochondrial ROS drive resistance to chemotherapy and immune-killing in hypoxic non-small cell lung cancer.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 39 citations in OpenAlex.
- Interleukin-1 receptor-associated kinase 1 controls chemoresistance and immuno-killing in non-small cell lung cancer.Signal transduction and targeted therapy · 2026Article
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- The transcription factor C/EBPβ promotes hyperglycemia-elicited glycolysis and liver cancer progression.Nature communications · 2026Article
- Establishing human immune system mice: application, opportunity, and challenges.Experimental & molecular medicine · 2026Review
- IGFL2 suppresses gastric cancer cell sensitivity to docetaxel by activating the Toll-like receptor signaling pathway.iScience · 2026Article
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Transcriptomic analysis of genes in bladder cancer patients with resistance to neoadjuvant chemoimmunotherapy.BMC cancer · 2026Article
- Bi-directional regulation between NAD/NAMPT and IFN-γ/PD-L1 axes via BRD4/IRF1 and mitochondrial respiration in metastatic cutaneous melanoma.Journal of experimental & clinical cancer research : CR · 2026Article
- MiR-4788 promotes NSCLC progression by targeting DLG5 to enhance mitochondrial function.Human genomics · 2026Article
- CD93-targeted resveratrol-loaded PLGA nanoparticles remodel CD8⁺ T cell metabolism through AIF-mediated oxidative phosphorylation to overcome lung cancer immunotherapy resistance.Journal of nanobiotechnology · 2026Article
- Exploiting porphyrin metabolism to inhibit angiogenesis.Angiogenesis · 2026Article
- Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy.Communications biology · 2026Article
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- Targeting shared mechanisms of cisplatin resistance and metastasis in lung cancer for novel therapeutic strategies.Discover oncology · 2026Review
- Extracellular vesicle-like particles fromFrontiers in pharmacology · 2026Article
- Targeting Oxidative and Nitrosative Stress: Mechanistic Insights and Therapeutic Strategies for Radiation-Induced Lung Injury.Journal of inflammation research · 2026Review
- Translational potential of γδ T cells in hematologic diseases: from immunobiology to therapeutic innovation.Frontiers in immunology · 2026Review
- Effects of Chronic Intermittent Hypoxia and Subsequent Normoxic Recovery on Renal Senescence and the PI3K/Akt/P21 Pathway in Rats.International journal of nephrology and renovascular disease · 2026Article
- CEBPB emerges as a key regulatory factor in human cancers through diverse molecular mechanisms and clinical implications.Discover oncology · 2025Review
- Role of Advanced Glycation End Products and Mitohormesis in Cancer Development and Progression.Antioxidants (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSolid tumors subjected to intermittent hypoxia are characterized by resistance to chemotherapy and immune-killing by effector T-lymphocytes, particularly tumor-infiltrating Vγ9Vδ2 T-lymphocytes. The molecular circuitries determining this double resistance are not known.
methodsWe analyzed a panel of 28 human non-small cell lung cancer (NSCLC) lines, using an in vitro system simulating continuous and intermittent hypoxia. Chemosensitivity to cisplatin and docetaxel was evaluated by chemiluminescence, ex vivo Vγ9Vδ2 T-lymphocyte expansion and immune-killing by flow cytometry. Targeted transcriptomics identified efflux transporters and nuclear factors involved in this chemo-immuno-resistance. The molecular mechanism linking Hypoxia-inducible factor-1α (HIF-1α), CCAAT/Enhancer Binding Protein-β (C/EBP-β) isoforms LAP and LIP, ABCB1, ABCC1 and ABCA1 transporters were evaluated by immunoblotting, RT-PCR, RNA-IP, ChIP. Oxidative phosphorylation, mitochondrial ATP, ROS, depolarization, O
resultsBy up-regulating ABCB1 and ABCC1, and down-regulating ABCA1, intermittent hypoxia induced a stronger chemo-immuno-resistance than continuous hypoxia in NSCLC cells. Intermittent hypoxia impaired the electron transport chain and reduced O
conclusionsThe impairment of mitochondrial metabolism induced by intermittent hypoxia increases the ROS-dependent stabilization of HIF-1α/LAP complex in NSCLC, producing chemo-immuno-resistance. Clinically used mitochondrial ROS scavengers may counteract such double resistance. Moreover, we suggest C/EBP-β LAP as a new predictive and prognostic factor in NSCLC patients.
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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.