ArticleCell division2016
Interferon gamma-induced apoptosis of head and neck squamous cell carcinoma is connected to indoleamine-2,3-dioxygenase via mitochondrial and ER stress-associated pathways.
Article in Cell division, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The immunotherapeutic role of indoleamine 2,3-dioxygenase in head and neck squamous cell carcinoma: A systematic review.Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery · 2021Pooled it
- Review
- Multi-omics insights into the molecular signature and prognosis of hypopharyngeal squamous cell carcinoma.Communications biology · 2025Article
- The aryl hydrocarbon receptor controls IFN-γ-induced immune checkpoints PD-L1 and IDO via the JAK/STAT pathway in lung adenocarcinoma.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Comprehensive transcriptomic analysis integrating bulk and single-cell RNA-seq with machine learning to identify and validate mitochondrial unfolded protein response biomarkers in patients with ischemic stroke.Frontiers in cell and developmental biology · 2025Article
- The Aryl Hydrocarbon Receptor Controls IFNγ-Induced Immune Checkpoints PD-L1 and IDO via the JAK/STAT Pathway in Lung Adenocarcinoma.bioRxiv : the preprint server for biology · 2024Article
- Effective Radiosensitization of HNSCC Cell Lines by DNA-PKcs Inhibitor AZD7648 and PARP Inhibitors Talazoparib and Niraparib.International journal of molecular sciences · 2024Article
- Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells.Frontiers in pharmacology · 2024Review
- Article
- Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck.Oral oncology · 2022Article
- STAT1 is regulated by TRIM24 and promotes immunosuppression in head and neck squamous carcinoma cells, but enhances T cell antitumour immunity in the tumour microenvironment.British journal of cancer · 2022Article
- The mitochondrial unfolded protein response (UPRJournal of hematology & oncology · 2022Review
- Article
- IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells.Oncoimmunology · 2021Article
- Melanoma stem cell maintenance and chemo-resistance are mediated by CD133 signal to PI3K-dependent pathways.Oncogene · 2020Article
- Article
- Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma.Cancer cell international · 2020Article
- p38 Expression and Modulation of STAT3 Signaling in Oral Cancer.Pathology oncology research : POR · 2020Article
- Immunomodulatory aspects in the progression and treatment of oral malignancy.The Japanese dental science review · 2019Review
- Mechanisms of IFNalpha-1a-Induced Apoptosis in a Laryngeal Cancer Cell Line.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor response to immunotherapy is the consequence of a concerted crosstalk between cytokines and effector cells. Interferon gamma (IFNγ) is one of the common cytokines coordinating tumor immune response and the associated biological consequences. Although the role of IFNγ in the modulation of tumor immunity has been widely documented, the mechanisms regulating IFNγ-induced cell death, during the course of immune therapy, is not described in detail.
resultsIFNγ triggered apoptosis of CLS-354 and RPMI 2650 cells, enhanced the protein expression and activation of indoleamine 2,3-dioxygenase (IDO), and suppressed the basal expression of heme oxygenase-1(HO-1). Interestingly, IFNγ induced the loss of mitochondrial membrane potential (Δψm) and increased accumulation of reactive oxygen species (ROS). The cytokine also induced the activation of Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT)1, apoptosis signal-regulating kinase 1 (ASK1), p38, c-jun-N-terminal kinase (JNK) and NF-κB pathways and the transcription factors STAT1, interferon regulatory factor 1 (IRF1), AP-1, ATF-2, NF-κB and p53, and expression of Noxa protein. Furthermore, IFNγ was found to trigger endoplasmic reticulum (ER) stress as evidenced by the cleavage of caspase-4 and activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol-requiring-1α (IRE1α) pathways. Using specific inhibitors, we identified a potential role for IDO as apoptotic mediator in the regulation of IFNγ-induced apoptosis of head and neck squamous cell carcinoma (HNSCC) cells via Noxa-mediated mitochondrial dysregulation and ER stress.
conclusionIn addition to the elucidation of the role of IDO in the modulation of apoptosis, our study provides new insights into the molecular mechanisms of IFNγ-induced apoptosis of HNSCC cells during the course of immune therapy.
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