Mononuclear phagocytes in head and neck squamous cell carcinoma

The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear phagocyte system. The aim of this review is to study the interactions between mononuclear phagocytes and head and neck squamous cell carcinoma tissue. The role of inflammation in tumours and the cytokine interleukin-6 will be highlighted. Future therapy strategies in the treatment of head and neck cancer might be directed towards mononuclear phagocytes and their cytokine production

Generic Quality of Life in persons With Hearing Loss: A Systematic Litterature Review

Background To the best of our knowledge, no empirically based consensus has been reached as to if, and to what extent, persons with hearing loss (HL) have reduced generic Quality of life (QoL). There seems to be limited knowledge regarding to what extent a hearing aid (HA) would improve QoL. The main aim of the present study was to review studies about the relationship between HL and QoL. A supporting aim was to study the association between distress and HL. Methods Literature databases (Cinahl, Pub Med and Web of Science) were searched to identify relevant journal articles published in the period from January 2000 to March 17, 2016. We performed a primary search pertaining to the relationship between HL, HA and QoL (search number one) followed by a supporting search pertaining to the relationship between distress/mood/anxiety and HL (search number two). After checking for duplications and screening the titles of the papers, we read the abstracts of the remaining papers. The most relevant papers were read thoroughly, leaving us with the journal articles that met the inclusion criteria. Results Twenty journal articles were included in the present review: 13 were found in the primary search (HL and QoL), and seven in the supporting search (HL and distress). The literature yields equivocal findings regarding the association between generic QoL and HL. A strong association between distress and HL was shown, where distressed persons tend to have a lowered generic QoL. It is suggested that QoL is lowered among HL patients. Some studies suggest an increased generic QoL following the use of HA, especially during the first few months after initiation of treatment. Other studies suggest that HA use is one of several possible factors that contribute to improve generic QoL. Conclusions The majority of the studies suggest that HL is associated with reduced generic QoL. Using hearing aids seem to improve general QoL at follow-up within the first year. HL is a risk factor for distress. Further research is needed to explore the relationship between HL and generic QoL, in addition to the importance of influencing variables on this relationship.publishedVersio

The acute phase reaction and its prognostic impact in patients with head and neck squamous cell carcinoma: Single biomarkers including c-reactive protein versus biomarker profiles

C-reactive protein (CRP) has a prognostic impact in head and neck squamous cell carcinoma (HNSCC). However, the acute phase reaction involves many other proteins depending on its inducing events, including various cytokines that can function as reaction inducers. In the present study, we compared the pretreatment acute phase cytokine profile for 144 patients with potentially curative HNSCC. We investigated the systemic levels of interleukin (IL)6 family mediators (glycoprotein (gp130), IL6 receptor (R)α, IL6, IL27, IL31, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), IL1 subfamily members (IL1R antagonist (A), IL33Rα), and tumor necrosis factor (TNF)α. Patient subsets identified from this 10-mediator profile did not differ with regard to disease stage, human papilloma virus (HPV) status, CRP levels, or death cause. Increased CRP, IL6, and IL1RA levels were independent markers for HNSCC-related death in the whole patient population. Furthermore, gp130, IL6Rα, and IL31 were suggested to predict prognosis among tumor HPV-negative patients. Only IL6 predicted survival in HPV-positive patients. Finally, we did a clustering analysis of HPV-negative patients based on six acute phase mediators that showed significant or borderline association with prognosis in Kaplan–Meier analyses; three subsets could then be identified, and they differed in survival (p < 0.001). To conclude, (i) HPV-negative and HPV-positive HNSCC patients show similar variations of their systemic acute phase profiles; (ii) the prognostic impact of single mediators differs between these two patient subsets; and (iii) for HPV-negative patients, acute phase profiling identifies three patient subsets that differ significantly in survival.publishedVersio

Maturation of monocyte derived dendritic cells with OK432 boosts IL-12p70 secretion and conveys strong T-cell responses

Background: Design of tumour specific immunotherapies using the patients’ own dendritic cells (DC) is a fast advancing scientific field. The functional qualities of the DC generated in vitro are critical, and today’s gold standard for maturation is a cytokine cocktail consisting of IL-1b, IL-6, TNF-a and PGE2 generating cells lacking IL- 12p70 production. OK432 is an immunotherapeutic agent derived from killed Streptococcus pyogenes that has been used clinically to treat malignant and benign neoplasms for decades. Methods: In this study, we analysed the effects of OK432 on DC maturation, DC migration, cytokine and chemokine secretion as well as T-cell stimulatory capacity, and compared it to the cytokine cocktail alone and combinations of OK432 with the cytokine cocktail. Results: OK432 induced a marked up-regulation of CD40 on the cell surface as well as a strong inflammatory response from the DC with significantly more secretion of 19 different cytokines and chemokines compared to the cytokine cocktail. Interestingly, secretion of IL-15 and IL-12p70 was detected at high concentrations after maturation of DC with OK432. However, the OK432 treated DC did not migrate as well as DC treated with cytokine cocktail in a transwell migration assay. During allogeneic T-cell stimulation OK432 treated DC induced proliferation of over 50 percent of CD4 and 30 percent of CD8 T-cells for more than two cell divisions, whereas cytokine cocktail treated DC induced proliferation of 12 and 11 percent of CD4 and CD8 T-cells, respectively. Conclusions: The clinically approved compound OK432 has interesting properties that warrants its use in DC immunotherapy and should be considered as a potential immunomodulating agent in cancer immunotherapy

Hearing as an Independent Predictor of Postural Balance in 1075 Patients Evaluated for Dizziness

Objective To evaluate the association between hearing and postural balance. Study Design Retrospective cross-sectional study. Setting Tertiary care otolaryngology clinic. Subjects and Methods Patients examined for suspected vestibular disorder were included in this study. The outcome variable was postural sway measured by static posturography during quiet standing with eyes closed. The predictor variable was pure-tone average hearing threshold on the best hearing ear at 0.5, 1, 2, and 3 kHz. Covariates were age, sex, and vestibular disease or vestibular asymmetry assessed by bithermal caloric irrigation. Results In total, 1075 patients were included. Increased hearing threshold was a strong predictor of increased postural sway (path length) after correcting for age and sex. A 10-dB increase in hearing loss on the best hearing ear predicted a mean 6.0% increase in path length (confidence interval, 2.9%-9.3%, P < .001). Of the covariates, increasing age (P < .001) and male sex (P = .009) were significant predictors of increased postural sway. The effect of increased hearing threshold was also significant after adjusting for vestibular disease. Conclusion Increased hearing threshold was an independent predictor of increased postural instability, and this effect was strongest for the best hearing ear. Unilateral vestibular disease did not seem to explain this association between hearing and postural balance. Reduced hearing is associated with impaired balance, and interventions to prevent falls should be considered for patients at risk.acceptedVersio

Long-Term Survival in 1,931 Patients With Dizziness: Disease- and Symptom-Specific Mortality

Objective: To evaluate mortality among patients referred for suspected vestibular disorder and to examine whether specific symptoms or disorders predict long-term survival among patients with dizziness or vertigo. Study Design: Retrospective cohort study. Methods: This retrospective cohort study analyzed long-term survival data. Consecutive patients examined for suspected vestibular disease at an otolaryngology clinic completed a detailed questionnaire regarding symptoms and comorbidities. Results: The study included 1,931 patients. Their mean age (standard deviation) was 50.5 (16.5) years, and 60% were women. The mean follow-up period was 20.6 years (range, 15.3–27.5 years). The standardized mortality ratio for the entire cohort compared with the Norwegian age- and sex-matched population was 1.03 (95% confidence interval [CI]: 0.94–1.12), illustrating no difference in overall survival. Patients with a cerebrovascular cause of dizziness had higher mortality in adjusted Cox regression analyses (hazard ratio [HR] 1.56, 95% CI: 1.11–2.19), whereas patients reporting periodic or short attacks of dizziness had lower mortality (HR 0.62 [0.50–0.77] and 0.76 [0.63–0.93], respectively). Reported unsteadiness between dizziness attacks was associated with higher mortality with an HR of 1.30 (95% CI: 1.08–1.57). Conclusion: This long-term study found comparable mortality rates between patients evaluated for suspected vestibular disorder and that of the general population. However, subgroup analyses showed reduced mortality in patients with periodic or short attacks of dizziness and increased mortality in patients with unsteadiness between attacks or cerebrovascular causes of dizziness. The time course of vestibular symptoms should be determined, and thorough evaluation including fall risk and comorbidities must be considered in patients with nonepisodic symptoms.publishedVersio

Serum levels of the IL-6 family of cytokines predict prognosis in renal cell carcinoma (RCC)

Purpose An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival. Methods A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. The patients were followed-up for 10 years. The morning before surgery blood was sampled and serum frozen, with levels of IL-6, IL-27, IL-31, OSM, CNTF, IL-6Rα and gp130 determined. Results Among patients with the highest quartile of IL-6 (> 8 pg/ml) (n = 29), six of nine who had metastasis at diagnosis had such high IL-6 values. Among presumed radically treated patients, a high IL-6 and IL-27 strongly predicted recurrence. In particular, the predictions among patients with large (diameter > 7 cm) tumors were excellent regarding both IL-6 and IL-27 values. High gp130 serum levels predicted an overall survival (OS) among RCC patients with large tumors. Patients with a high IL-6 exhibited a strong expression of IL-6 in endothelial- and vascular smooth muscle cells. Moreover, the level of intra-tumoral CD3-positive cells predicted survival. Conclusions IL-6 and IL-27 seem to play a role in RCC biology. IL-6 enables the pinpointing of metastatic condition at diagnosis, as well as together with IL-27, the predicting of survival and recurrence. Endothelial cells and vascular smooth muscle cells are both suggested as important sources of IL-6.publishedVersio

The levels of IL-6 and soluble IL-33R are increased in the renal vein during surgery for clear cell renal cell carcinoma

Purpose The main aim was to map serum levels of IL-1/IL-6 family cytokines and relevant receptors from serum samples taken across treatment in patients with Renal Cell Carcinoma (RCC). Additionally, we explored the possible interactions between these measurements, immunohistochemistry and intratumoral blood flow. Methods We included 40 patients undergoing open surgery for renal tumors. Blood samples were collected before, during (taken simultaneously from a peripheral site and the renal vein (RV) before clamping) and after surgery. Samples were analyzed for IL-6, IL-27, IL-31, OSM, TNF-α, serum (s)-gp130, s-IL-6Rα, s-IL-33R, IL-1Rα and VEGF. All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. Immunohistochemistry for the CCRCC group included expression of IL-6/IL-6R. Intratumoral blood flow was determined by calculating intratumoral contrast enhancement on preoperative computerized tomography (CT) imaging. Results In the CCRCC patients, the intraoperative RV concentration of IL-6 was significantly higher than in both the preoperative and postoperative samples (p = 0.005 and p = 0.032, respectively). Furthermore, the intraoperative ratio showed significantly higher levels of IL-6 in the RV than in the simultaneously drawn peripheral sample. Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. Increased blood flow in the CCRCC tumors predicted increased IL-6 levels in the RV (p < 0.001). The other cytokines and receptors showed an overall stability across the measurements. However, the intraoperative ratios of IL-33R and gp130 showed significantly higher levels in the RV. Conclusion Serum levels of IL-6 increased during surgery. Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. Other studied cytokines/receptors were remarkably stable across all measurements.publishedVersio

Functional-structural reorganisation of the neuronal network for auditory perception in subjects with unilateral hearing loss: Review of neuroimaging studies.

This paper aims to provide a review of studies using neuroimaging to measure functional-structural reorganisation of the neuronal network for auditory perception after unilateral hearing loss

Tumor infiltration levels of CD3, Foxp3 (+) lymphocytes and CD68 macrophages at diagnosis predict 5-year disease-specific survival in patients with oropharynx squamous cell carcinoma

Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses. We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established. From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (−) patients. High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (−) patients.publishedVersio