Hypoxia and HNSCC

BACKGROUND: Head and neck squamous cancer (HNSCC) presents variable phenotype and progression features. Clinically applicable, high-accuracy multifactorial prognostic models for HNSCC survival outcomes are warranted and an active area of research. This study aimed to construct a comprehensive prognostic tool for HNSCC overall survival by integrating cancer driver genes with tumor clinical and phenotype information. METHODS: Key overall survival-related cancer driver genes were screened from among main effector and reciprocal gene pairs using TCGA data using univariate Cox proportional hazard regression analysis...

Tumor necrosis is a recurrent characteristic of head and neck squamous cell carcinomas (HNSCCs). There is a need for more investigations on the influence of biomolecules released by these necrotic foci in the HNSCC tumor microenvironment. It is suspected that a fraction of the biomolecules released by necrotic cells are damage-associated molecular patterns (DAMPs), which are known to be natural endogenous ligands of Toll-like receptors (TLRs), including, among others, proteins and nucleic acids. However, there has been no direct demonstration that biomolecules released by HNSCC necrotic cells can activate TLRs...

In the tumor milieu of head and neck squamous cell carcinoma (HNSCC), distinct B cell subpopulations are present, which exert either pro- or anti-tumor activities. Multiple factors, including hypoxia, cytokines, interactions with tumor cells, and other immune infiltrating lymphocytes (TILs), alter the equilibrium between the dual roles of B cells leading to cancerogenesis. Certain B cell subsets in the tumor microenvironment (TME) exhibit immunosuppressive function. These cells are known as regulatory B (Breg) cells...

Mitochondria play a crucial role in the occurrence and development of tumors. We used mitochondria-related genes for consistent clustering to identify three stable molecular subtypes of head and neck squamous cell carcinoma (HNSCC) with different prognoses, mutations, and immune characteristics. Significant differences were observed in clinical characteristics, immune microenvironment, immune cell infiltration, and immune cell scores. TP53 was the most significantly mutated; cell cycle-related pathways and tumorigenesis-related pathways were activated in different subtypes...

BACKGROUND: The advantages of radiotherapy for head and neck squamous cell carcinoma (HNSCC) depend on the radiation sensitivity of the patient. Here, we established and verified radiological factor-related gene signature and built a prognostic risk model to predict whether radiotherapy would be beneficial. METHODS: Data from The Cancer Genome Atlas, Gene Expression Omnibus, and RadAtlas databases were subjected to LASSO regression, univariate COX regression, and multivariate COX regression analyses to integrate genomic and clinical information from patients with HNSCC...

BACKGROUND: Tumor hypoxia is associated with resistance to radiotherapy and chemotherapy. In head and neck squamous cell carcinoma (HNSCC), nimorazole, an oxygen mimic, combined with radiotherapy (RT) enabled to improve loco-regional control (LRC) in some patients with hypoxic tumors but it is unknown whether this holds also for radiochemotherapy (RCTx). Here, we investigated the impact of nimorazole combined with RCTx in HNSCC xenografts and explored molecular biomarkers for its targeted use...

Patients with human papillomavirus-negative head and neck squamous cell carcinoma (HPV-negative HNSCC) have worse outcomes than HPV-positive HNSCC. In our study, we used a published dataset and investigated the microbes enriched in molecularly classified tumor groups. We showed that microbial signatures could distinguish Hypoxia/Immune phenotypes similar to the gene expression signatures. Furthermore, we identified three highly-correlated microbes with immune processes that are crucial for immunotherapy response...

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia salmonea (AS), linked to the genus Taiwanofungus, is a medicinal fungus, and exhibits anti-inflammatory, anti-oxidant, and tumor inhibiting properties. AIM OF THE STUDY: In this study, we investigated the metabolic reprogramming and anti-metastasis/epithelial-mesenchymal transition (EMT) effects of AS exposure in Twist-overexpressing head and neck squamous cell carcinoma (HNSCC, OECM-1 and FaDu-Twist) cells. MATERIALS AND METHODS: MTT assay, Western blot, migration/invasion assay, immunofluorescence, glucose uptake assay, lactate assay, oxygen consumption rate (OCR)/Extracellular acidification rate (ECAR) assay, Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS), and qRT-PCR experimental techniques were used to evaluate the therapeutic potential of AS treatment in HNSCC cells...

Despite refinements to diagnostic and therapeutic approaches over the last two decades, the outcome of patients with head and neck squamous cell carcinoma (HNSCC) has not shown substantial improvements, especially regarding those with advanced-stage disease. Angiogenesis is believed to be a turning point in the development of solid tumors, being a premise for mass growth and potential distant dissemination. Cancer-induced angiogenesis is a result of increased expression of angiogenic factors, decreased expression of anti-angiogenic factors, or a combination of both...

UNLABELLED: Head and neck squamous cell carcinoma (HNSCC) has one of the most hypoxic and immunosuppressive tumor microenvironments (TME) among solid tumors. However, there is no proven therapeutic strategy to remodel the TME to be less hypoxic and proinflammatory. In this study, we classified tumors according to a Hypoxia-Immune signature, characterized the immune cells in each subgroup, and analyzed the signaling pathways to identify a potential therapeutic target that can remodel the TME...

Hypoxia in head and neck tumors has proven to be predictive of outcomes. Current hypoxia signatures have failed for patient treatment selection. In a recent study, the authors identified a hypoxia methylation signature as a more robust biomarker in HNSCC and shed light into the mechanism of hypoxia-mediated treatment resistance.

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BACKGROUND: Both microRNA-21-5p (miR-21) and the tumor microenvironment, including hypoxia and cancer-associated fibroblasts (CAFs), play a vital role in head and neck squamous cell carcinoma (HNSCC), but whether there is an interaction and the specific regulatory mechanism between them in the process of metastasis is still unclear. In this study, we aimed to elucidate the connection and regulatory mechanism of miR-21, hypoxia, and CAFs in HNSCC metastasis. METHODS: The underlying mechanisms of hypoxia inducible factor 1 subunit alpha (HIF1α) regulating miR-21 transcription, promoting exosome secretion, CAFs activation, tumor invasion, and lymph node metastasis were determined through quantitative real-time PCR, immunoblotting, transwell, wound healing, immunofluorescence, ChIP, electron microscopy, nanoparticle tracking analysis, dual-luciferase reporter assay, co-culture model and xenografts experiments...

Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone...

PURPOSE: Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. EXPERIMENTAL DESIGN: A DNA-methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES)...

Diffuse reflectance spectroscopy (DRS) is a powerful tool for quantifying optical and physiological tissue properties such as hemoglobin oxygen saturation and vascularity. DRS is increasingly used clinically for distinguishing cancerous lesions from normal tissue. However, its widespread clinical acceptance is still limited due to uncontrolled probe-tissue interface pressure that influences reproducibility and introduces operator-dependent results. In this clinical study, we assessed and validated a pressure-sensing and automatic self-calibration DRS in patients with suspected head and neck squamous cell carcinoma (HNSCC)...

Tumor budding (TB), a microscopic finding in the stroma ahead of the invasive fronts of tumors, has been well investigated and reported as a prognostic marker in head and neck squamous cell carcinoma (HNSCC). Epithelial-mesenchymal transition (EMT) is a crucial step in tumor progression and metastasis, and its status cannot be distinguished from TB. The current understanding of partial EMT (p-EMT), the so-called halfway step of EMT, focuses on the tumor microenvironment (TME). Although this evidence has been investigated, the clinicopathological and biological relationship between TB and p-EMT remains debatable...

Tumour cells under hypoxia tend to modulate the number and contents of extracellular vesicles (EVs) to regulate the tumour microenvironment (TME) and thus promote tumour progression. However, the mechanism of how hypoxia influences the secretion of EVs remains to be elucidated. Here, we confirm the increased production of EVs in head and neck squamous cell carcinoma (HNSCC) cells under hypoxia, where endosome-derived EVs are the main subtype affected by insufficient O2 . The accumulation of hypoxia-inducible factor-1α (HIF-1α) under hypoxia directly downregulates the expression of ATP6V1A, which is pivotal to maintain the homeostasis of lysosomes...

BACKGROUND: The 5-year survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remains  < 50%. Hypoxia patterns are a hallmark of HNSCC that are associated with its occurrence and progression. However, the precise role of hypoxia during HNSCC, such as the relationship between hypoxia, tumor immune landscape and cell communication orchestration remains largely unknown. The current study integrated data from bulk and single-cell RNA sequencing analyses to define the relationship between hypoxia and HNSCC...

Head and neck cancer is a malignant tumour with a high mortality rate characterized by late diagnosis, high recurrence and metastasis rates, and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer. Various factors are involved in the occurrence and development of HNSCC, including external inflammatory stimuli and oncogenic viral infections. In recent years, studies on the regulation of cell death have provided new insights into the biology and therapeutic response of HNSCC, such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and recently the newly discovered cuproptosis...