Hypoxia and HNSCC

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) presents a significant clinical challenge, particularly due to its high propensity for locoregional recurrence. Current research underscores the need to unravel the complex interactions within the tumor microenvironment. This study addresses the critical gap in understanding how FOS modulates the immune landscape in HNSCC, with a focus on its influence on fibroblast and myeloid cell dynamics. METHODS: Employing a comprehensive approach, we analyzed tissue samples from HNSCC patients and adjacent non-cancerous tissues using bulk RNA sequencing complemented by in-depth bioinformatics analyses, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and immune infiltration assessment...

The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis...

BACKGROUND: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in phase 2 trials. In this context, the addition of radio- and chemotherapy is being reconsidered. Therefore, a better understanding of the tumor-biologic effects of neoadjuvant RCT would be beneficial...

BACKGROUND: Tumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Current positron emission tomography-based hypoxia imaging techniques are not routinely available in many centres. We investigated if an alternative technique called oxygen-enhanced magnetic resonance imaging (OE-MRI) could be performed in HNSCC. METHODS: A volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was implemented on 1...

Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia-activated prodrugs (HAPs)...

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) patients suffer from frequent local recurrences that negatively impact on prognosis. Hence, distinguishing tumor and normal tissue is of clinical importance as it may improve the detection of residual tumor tissue in surgical resection margins and during imaging-based surgery planning. Differences in O2 consumption (OC) can be used to this aim, as they provide options for improved surgical, image-guided approaches. METHODS: In the present study, the potential of a fluorescent sensor foil-based technology to quantify OC in HNSCC was evaluated in an in vitro 3D model and in situ in patients...

Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and hypoxia are associated with radioresistance. The goal of this study is to study the synergy of anti-HER2, trastuzumab, and anti-EGFR, cetuximab, and characterize the tumor microenvironment components that may lead to increased radiation sensitivity with dual anti-HER2/EGFR therapy in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography (PET) imaging ([89 Zr]-panitumumab and [89 Zr]-pertuzumab) was used to characterize EGFR and HER2 in HNSCC cell line tumors...

BACKGROUND AND PURPOSE: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint. MATERIALS AND METHODS: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study...

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents one of the most malignant cancers worldwide, with poor survival. Experimental evidence implies that glycolysis/hypoxia is associated with HNSCC. In this study, we aimed to construct a novel glycolysis-/hypoxia-related gene (GHRG) signature for survival prediction of HNSCC. METHODS: A multistage screening strategy was used to establish the GHRG prognostic model by univariate/least absolute shrinkage and selection operator (LASSO)/step multivariate Cox regressions from The Cancer Genome Atlas cohort...

Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. This study aims to investigate the role of hypoxia-related genes (HRG) in the immune landscape, treatment response, and prognosis of head and neck squamous cell carcinoma (HNSCC). The transcriptome and clinical data of HNSCC were downloaded from TCGA and GEO databases, and HNSCC molecular subtypes were identified using non-negative matrix factorization (NMF) clustering. Prognostic models were constructed using univariate, Lasso, and multivariate Cox regression analyses...

Head and neck squamous cell carcinoma (HNSCC) remains a formidable clinical challenge due to its high recurrence rate and limited targeted therapeutic options. This study aims to elucidate the role of tensin 4 (TNS4) in the pathogenesis of HNSCC across clinical, cellular, and animal levels. We found a significant upregulation of TNS4 expression in HNSCC tissues compared to normal controls. Elevated levels of TNS4 were associated with adverse clinical outcomes, including diminished overall survival. Functional assays revealed that TNS4 knockdown attenuated, and its overexpression augmented, the oncogenic capabilities of HNSCC cells both in vitro and in vivo ...

PURPOSE: To assess the robustness of prognostic biomarkers and molecular tumour subtypes developed for patients with head and neck squamous cell carcinoma (HNSCC) on cell-line derived HNSCC xenograft models, and to develop a novel biomarker signature by combining xenograft and patient datasets. MATERIALS AND METHODS: Mice bearing xenografts (n=59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (n=242) of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) were included...

In solid tumors like head and neck cancer (HNC), chronic and acute hypoxia have serious adverse clinical consequences including poorer overall patient prognosis, enhanced metastasis, increased genomic instability, and resistance to radiation-, chemo-, or immuno-therapies. However, cells in the two-dimensional monolayer cultures typically used for cancer drug discovery experience 20%-21% O2 levels (normoxic) which are 4-fold higher than O2 levels in normal tissues and ≥10-fold higher than in the hypoxic regions of solid tumors...

INTRODUCTION: Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance...

PURPOSE: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689)...

BACKGROUND: Immune checkpoint inhibitors of programmed cell death protein 1 (PD-1) represent a significant breakthrough in treating head and neck squamous cell carcinoma (HNSCC), with long-lasting responses and prolonged survival observed in first- and second-line therapy. However, this is observed in < 20% of patients and high primary/secondary resistance may occur. The primary objective of the identification of predictive factors for the response to anti-PD-1 immunotherapy in head and neck squamous cell carcinoma (IPRICE) study is to identify predictive factors of response to anti-PD-1 immunotherapy...

BACKGROUND: Adverse pathological features following surgery in head and neck squamous cell carcinoma (HNSCC) are strongly associated with survival and guide adjuvant therapy. We investigated molecular changes associated with these features. METHODS: We downloaded data from the Cancer Genome Atlas and Cancer Proteome Atlas HNSCC cohorts. We compared tumors positive versus negative for perineural invasion (PNI), lymphovascular invasion (LVI), extracapsular spread (ECS), and positive margins (PSM), with multivariable analysis...

Head and neck squamous cell carcinoma (HNSCC) is a disease associated with a severe mortality and high risk of distant metastasis and local recurrence. Currently, surgery and radiotherapy are the main treatment modes, however, therapeutic efficacy of radiotherapy is linked to tumor resistance. Hypoxia has been shown to affect outcome of radiotherapy in HNSCC patients. The aim of this study was to verify the expression of the previously identified hypoxia-responsive genes (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14) in HNSCC patient material as well as assess their prognostic potential...

Head and neck squamous cell cancer (HNSCC) is one of the ten most common malignant neoplasms, characterized by an aggressive course, high recurrence rate, poor response to treatment, and low survival rate. This creates the need for a deeper understanding of the mechanisms of the pathogenesis of this cancer. The tumor microenvironment (TME) of HNSCC consists of stromal and immune cells, blood and lymphatic vessels, and extracellular matrix. It is known that HNSCC is characterized by complex relationships between cancer cells and TME components...

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of head and neck, which seriously threatens human life and health. However, the mechanism of hypoxia-associated genes (HAGs) in HNSCC remains unelucidated. This study aims to establish a hypoxia-associated gene signature and the nomogram for predicting the prognosis of patients with HNSCC. METHODS: Previous literature reports provided a list of HAGs. The TCGA database provided genetic and clinical information on HNSCC patients...