Nuclear S100A7 Is Associated with Poor Prognosis in Head and Neck Cancer

Tissue proteomic analysis of head and neck squamous cell carcinoma (HNSCC) and normal oral mucosa using iTRAQ (isobaric tag for relative and absolute quantitation) labeling and liquid chromatography-mass spectrometry, led to the identification of a panel of biomarkers including S100A7. In the multi-step process of head and neck tumorigenesis, the presence of dysplastic areas in the epithelium is proposed to be associated with a likely progression to cancer; however there are no established biomarkers to predict their potential of malignant transformation. This study aimed to determine the clinical significance of S100A7 overexpression in HNSCC.Immunohistochemical analysis of S100A7 expression in HNSCC (100 cases), oral lesions (166 cases) and 100 histologically normal tissues was carried out and correlated with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients. Overexpression of S100A7 protein was significant in oral lesions (squamous cell hyperplasia/dysplasia) and sustained in HNSCC in comparison with oral normal mucosa (p(trend)<0.001). Significant increase in nuclear S100A7 was observed in HNSCC as compared to dysplastic lesions (p = 0.005) and associated with well differentiated squamous cell carcinoma (p = 0.031). Notably, nuclear accumulation of S100A7 also emerged as an independent predictor of reduced disease free survival (p = 0.006, Hazard ratio (HR = 7.6), 95% CI = 1.3-5.1) in multivariate analysis underscoring its relevance as a poor prognosticator of HNSCC patients.Our study demonstrated nuclear accumulation of S100A7 may serve as predictor of poor prognosis in HNSCC patients. Further, increased nuclear accumulation of S100A7 in HNSCC as compared to dysplastic lesions warrants a large-scale longitudinal study of patients with dysplasia to evaluate its potential as a determinant of increased risk of transformation of oral premalignant lesions

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health

Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study

<div><p>Background</p><p>Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS).</p><p>Methods and findings</p><p>The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18–90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9–66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17–60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16^BRIGHT CD62L^DIM neutrophils (82.07 x 10⁶/l ± 18.94 control versus 1,092 x 10⁶/l ± 165 trauma, <i>p</i> < 0.0005) and CD14⁺HLA-DR^low/− monocytes (34.96 x 10⁶/l ± 4.48 control versus 95.72 x 10⁶/l ± 8.0 trauma, <i>p</i> < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function.</p><p>Conclusions</p><p>Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.</p></div

Serum cytokine and chemokine concentrations post-trauma.

<p>Serum concentrations of IL-6 (A), IL-8 (B), G-CSF (C), IL-1Ra (D), TNF-α (E), and IL-10 (F) across time post-trauma. The number of patient and HC samples analysed is indicated below each time point. The horizontal line for HC data depicts the median value. **<i>p</i> < 0.005, ***<i>p</i> < 0.0005 versus HCs. G-CSF, granulocyte-colony stimulating factor; HC, healthy control; IL, interleukin; IL-1Ra, interleukin-1 receptor antagonist; TNF- α, tumour necrosis factor-alpha.</p

Evidence of NET formation during the ultra-early immune response to sterile traumatic injury.

<p>(A–B) Plasma concentrations (ng/ml) of nuclear (A) and mitochondrial (B) DNA across time post-trauma. The number of samples analysed is indicated below each time point. The horizontal line for HC data depicts the median value. *<i>p</i> < 0.05, ***<i>p</i> < 0.0005 versus HCs. (C–D) Western blots showing the levels of citrullinated histone H3 in plasma samples obtained from 9 trauma patients within 1 hour of injury (C) and in 3 trauma patients across the 3 postinjury time points (D). +ve CNT, positive control; HC, healthy control; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; NET, neutrophil extracellular trap.</p

Neutrophil surface phenotype.

<p>Neutrophil surface phenotype.</p

Illustrative odds ratios for development of MODS based on changes in values of NKT number.

<p>Illustrative odds ratios for development of MODS based on changes in values of NKT number.</p

Traumatic injury results in elevated percentages and absolute numbers of circulating CD14⁺HLA-DR^-/low immunosuppressive monocytes.

<p>(A) Representative flow cytometry plots depicting the percentage of CD14⁺HLA-DR^-/low monocytes (upper left quadrant) in a single HC and a trauma patient across time. (B–C) Prospective assessment of the percentage (B) and absolute number (C) of CD14⁺HLA-DR^-/low monocytes post-trauma. The number of samples analysed is indicated below each time point. The horizontal line for HC data depicts the median value. *<i>p</i> < 0.05, ***<i>p</i> < 0.0005 versus HC. HC, healthy control.</p