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Identification of the association between tissue biomarkers, their surrogates in blood and clinical features, could provide new diagnostic tools and facilitate adequate choices of therapeutic interventions for selected patients suffering from CRS. The aim of present study was the assessment of macrophages in the polyp tissue and monocytes in the peripheral blood in the course of CRSwNP, and their functional immunophenotype. We analyzed 31 patients with CRSwNP. Nasal mucosa tissue was obtained via functional endoscopic sinus surgery (FESS). The control group included 10 patients with deviated nasal septum (DNS). Fluorochrome stained cells were proceed to acquisition using FACS Canto flow cytometer, and the results were analyzed using the software FACS Diva. In our study, we observed a significantly higher level of CD80, CD274, CD273 and TLR1 in nasal polyps compared to blood samples from patients with CRSwNP. This finding may suggest the importance of the PD-1 pathway as a therapeutic target in CRS and an important role for TLR1 in nasal polyp formation and maintenance. Our results may provide some insight into potential future targets of recurrent nasal polyp treatment and contribute to a better understanding of the inflammatory process in Chronic Rhinosinusitis., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Objectives: PRAME (Preferentially Expressed Antigen in Melanoma) is a tumor-associated antigen recognized by immunocytes, and it induces cytotoxic T cell-mediated responses in melanoma. PRAME expression in tumors interferes with retinoic acid receptor (RAR) signaling thus promoting tumor progression. Here, we study PRAME expression in head and neck squamous cell carcinoma (HNSCC) to determine its potential clinical significance., Materials and Methods: PRAME expression in HNSCC was evaluated by immunohistochemistry in tissue microarrays of primary tumors (n=53), metastatic lymph nodes (n=8) and normal oral mucosa (n=11). Biopsies of dysplastic oral lesions (n=12) were also examined. PRAME expression levels in tissues were correlated with markers of poor prognosis in HNSCC. PRAME mRNA in HNSCC cell lines and in normal immortalized human keratinocytes (HaCaT cell line) was measured by qRT-PCR, and the protein expression by flow cytometry and western blots., Results: PRAME was expressed in HNSCC cell lines and HNSCC lesions. PRAME expression in dysplastic mucosa was variable. No or only weak expression was found in normal cells or tissues. PRAME expression levels significantly correlated with the tumor grade, size, nodal involvement and the clinical status of HNSCC patients., Conclusions: Elevated PRAME expression associates with clinicopathologic markers of poor outcome in HNSCC and might identify potential candidates with pre-cancerous lesions for chemoprevention with retinoids., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to analyze the properties of the immune cell microenvironment of regional lymph nodes (LNs) positive for lung cancer., Methods: Twenty-four patients operated on for stages T1 and T2 of the NSCLC, were enrolled in the study. Peripheral blood and LN tissue were obtained from different lymph node sites and levels. As a control, LN tissue was taken from patients diagnosed with emphysema or pneumothorax. The cells from randomly chosen LN were tested by multi-color flow cytometry. Separate portions of LN were snap-frozen and examined for the presence of cytokeratin positive cells (CK). Propensity for apoptosis, level of TCR zeta chain expression of T cells and the number and maturation status of dendritic cells were confronted with the presence of CK-positive cells., Results: The presence of metastases correlated with the downregulation of TCR zeta, especially CD8(+) T cells. The most striking feature was the reduction in the number of myeloid CD11c(+) dendritic cells in the LN of patients with LN metastases. This could be a reflection of the immunodeficient state observed in lung cancer patients. Even in the absence of metastases in the regional LN, the same type of changes in the LN microenvironment were observed in those LN located nearer the primary tumor., Conclusions: The preliminary results of this study suggest that this approach may be helpful as an independent tumor staging factor. It is also worth noting that part of the staging process could also be based on features describing the immune cells in the peripheral blood.

Adhesion of ovarian cancer cells to the peritoneal mesothelium is a key step in the malignant progression of the disease. In an in vitro study, we showed that the adherence of ovarian cancer cells (of the OVCAR-3, SKOV-3, and A2780 cell lines) to senescent human omentum-derived peritoneal mesothelial cells (HOMCs) was greater than to early passage cells. The process was mediated primarily by the increased interaction of the alpha5beta1 integrin on cancer cells with HOMC-associated fibronectin (FN). In comparison with early passage HOMCs, senescent cells exhibited increased FN mRNA expression levels and produced significantly more FN. To assess the effect of senescence-associated oxidative stress on FN release, HOMCs were rendered senescent by exposure to an oxidant, tert-butyl hydroperoxide. Treatment with tert-butyl hydroperoxide resulted in a significant increase in HOMC FN mRNA and protein expression levels. The effect of oxidative stress on FN synthesis was found to be mediated by transforming growth factor-beta1, whose signaling pathway was controlled at upstream and downstream levels by p38 MAPK. The activity of p38 MAPK increased markedly in senescent HOMCs. Treatment of HOMCs with antioxidants significantly attenuated senescence-associated increases in p38 MAPK activity, production of both transforming growth factor-beta1 and FN, and ovarian cancer cell adhesion. These data indicate that oxidative stress that accompanies senescence may increase FN production by HOMCs and thus facilitate binding and dissemination of ovarian cancer cells.

To address the question of in situ production of IL-1 alpha and IL-1 beta in proliferative and non-proliferative forms of human glomerulonephritis (GN), we performed immunocytochemical and in situ hybridization studies on renal biopsies from patients with mesangial IgA-GN (N = 38), idiopathic membranous GN (MGN; N = 12), minimal change disease (MCD; N = 9), focal segmental glomerulosclerosis (FSGS; N = 5) and acute endocapillary GN (AGN; N = 3). Normal kidneys (N = 10) served as controls. Concomitantly, the expression of IL-1 receptor type I (IL-1 RI), IL-1 receptor type II (IL-1 RII) and of IL-1 receptor antagonist (IL-1 RA) was analyzed. Antibodies against antigens expressed on podocytes (PP-44), endothelial cells (CD31) and monocytes/macrophages (CD11b, CD14, CD68) were applied to attribute the expression of IL-1/IL-1 related peptides to intrinsic glomerular and/or blood-derived infiltrating cells. Our results demonstrate that IL-1 RII is constitutively expressed on endothelial cells, and its expression can be induced in proximal tubular cells and in the interstitium. In diseased glomeruli podocytes are capable of producing IL-1 alpha/beta. In MGN and MCD/FSGS, the expression of both IL-1 forms is particularly noted in early stages of the disease and is not only accompanied by a marked reactivity for IL-1 RI, but also for IL-1 RA. In segmental sclerosing lesions in FSGS and in IgA-GN with marked glomerular proliferation and/or sclerosis, a reduced expression of the PP-44 antigen and a diminished ability of podocytes to produce IL-1/IL-1 related peptides are noted. These results suggest that intrinsic glomerular production of IL-1 may be of relevance for the protection of glomeruli from continuing injury.