Search

Although cancer associated fibroblast (CAF) heterogeneity is recognized in oral squamous cell carcinoma (OSCC), the phenotype and role of CAF subpopulations in OSCC is still unknown. This study aimed to develop a method to identify and spatially define CAF subpopulations on formalin fixed paraffin embedded (FFPE) tissues from primary OSCC. Imaging mass cytometry was used to identify 24 markers (E-cadherin, EGFR, Ki-67, α-SMA, CD140β, FAP, FSP-1/S100A4, CD90/Thy-1, integrin α-11, collagen-1, tenascin-C, caveolin-1, CD4, CD8a, CD16, CD20, CD68, CD163, FoxP3, granzyme B, CD31, podoplanin, CD146, and YAP-1) in HPV-negative OSCC lesions (n=5). Tissue images were segmented employing the Steinbock framework. Unsupervised clustering of single-cell data was carried out using a bioinformatics pipeline developed in R language. Unsupervised clustering identified several major cell types, with E-cadherin+ cells being the most abundant (30% and CD146+ being the least abundant cell type (0.62%). Among the immune component, CD4+ were most abundant (11.72%) followed by CD8+ (10.6%) and CD68+ (10.25%). Two clusters were negative for other major lineage markers and positive for stromal markers. These were defined as CAF-1 (high αSMA, CD140β, and CD90) and CAF-2 (high FAP and collagen-1). CAF-1 subtype was found closer to immune cells whereas CAF-2 were closely located to cancer cells. Based on integrin α-11, FSP-1/S100A4 and podoplanin these could be further dissected in 6 CAF clusters. The pipeline developed here shows promise for understanding clinical implications of CAF heterogeneity in clinical samples from large OSCC patient cohorts with FFPE tissues available in diagnostic biobanks. [ABSTRACT FROM AUTHOR]

Background: This study was performed in order to determine whether monocyte in vitro function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease.Methods: Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte in vitro interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis.Results: All patients, as a group, had higher in vitro monocyte responsiveness in terms of IL-6 (AS) (t = 2.03; p < 0.05) and MCP-1 (SFM) (t = 2.49; p < 0.05) compared to controls. Increased in vitro monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05-4.88; p < 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03-6.92; p < 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (chi = 4.0; p < 0.05).Conclusion: In HNSCC patients, changed monocyte in vitro response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors. [ABSTRACT FROM AUTHOR]

To examine the survival prediction of head and neck (H&N) Health Related Quality of Life (HRQoL) scores among successfully treated and cognitive functioning H&N squamous cell carcinoma (HNSCC) patients. Through structured interviews, self-reported questionnaires were given to 139 successfully treated HNSCC patients, 67±32months following diagnosis. HRQoL-scores, measured with the EORTC QLQ-H&N35 inventory, self-reported levels of neuroticism, avoidance focused coping, coping by suppression of competing activity, alcohol consumption, smoking status, and heart and lung disease, as well as gender, age, TNM-stage, and tumor site were determined. The mean observation period was 75±4months among the survivors. Twenty-four deaths were observed. A EORTC QLQ-H&N35 sum score, including a dichotomized version (HR 2.73-3.67), was predictive of survival, both directly and after adjustment for all of the above mentioned variables. The H&N HRQoL indices 'feeling ill', 'sexuality', 'open mouth', 'swallowing', and 'pain' specifically predicted survival. The dichotomized H&N HRQoL sum score compared the 4th upper quartile to the three lower quartiles, and a cut off value of 28.5 was designated. Analyses demonstrated that a high risk group with 33% mortality may include only one quarter of the patient population as opposed to 12.5% mortality among the other patients. Our findings indicate a unique survival prediction from EORTC QLQ-H&N35 sum scores in successfully treated HNSCC patients. HRQoL scores, in particular, related to oral health, predicted survival. Furthermore, HRQoL-scores may be a screening tool for identifying patients with high mortality risk. [ABSTRACT FROM AUTHOR]