IL-17 Producing Cells and RORγt mRNA Transcriptional Factor in Cirrhotic and HCC Egyptian Patients.

Retinoic acid-related orphan receptor gT (RORγT) is the orphan nuclear receptor that regulates the development of Th17 cells and the expression of IL-17. The differentiation of Th17 cells is associated with the upregulation of RORγT mRNA, and the mechanisms regulating that process in human cells are not well understood. RORγt as transcription factor was selectively expressed in Th17 cells and is regulated by STAT3. The relationship between Th17 cells and tumor immunopathology has been controversial. Aim of the study is to evaluate Th17 cells and RORγt transcriptional factor in cirrhotic, early and advanced HCC patients. Ninety patients were studied (30 cirrhotic, 30 early stage and 30 advanced stage HCC patients). They were recruited from the National Liver Institute, Menoufia University, and subjected to full clinical examination, investigations to detect liver cirrhosis, portal vein thrombosis and tumor staging. Peripheral blood mononuclear cells (PBMCs) were stimulated with cytosim, ionomycin and monensin, and surface (CD4-PE)as well as intracellular staining for Th17 (IL-17 FITC) was performed. Analysis of cells was carried out using FACS Calibur. RORγt mRNA expression in PBMCs was measured by real time RT- PCR. Cirrhotic patients showed increased Th17% cells, without significant change in RORγt mRNA as compared to early stage HCC. Advanced stage HCC patients showed significant increase of Th17 cells% and RORγt mRNA compared to studied patients group. Positive correlation of Th17 and RORγtmRNA was found with aminotransferases and bilirubin levels while, negative with serum albumin in advanced stage patients group (P < 0.001). Both markers were significantly increased with tumor size; RORγt mRNA increased with multiple tumor foci. In conclusion, Th17 cells and RORγt may be useful prognostic markers for advanced liver cirrhosis and HCC.

CD14(+) HLA-DR low/(-) monocytes as indicator of disease aggressiveness in B-cell non-Hodgkin lymphoma.

INTRODUCTION: This study aimed to assess the correlation between the percentage of CD14(+) HLA-DR(low/-) immunosuppressive monocytes, plasma arginase 1 level, and disease aggressiveness in patients with B-cell non-Hodgkin lymphoma. METHODS: Forty-two patients with B-cell non-Hodgkin lymphoma and 20 healthy volunteers were enrolled in this study. Peripheral blood CD14+ HLA-DR(low/-) monocytes were detected by Flow cytometry, and their correlation with disease relapse and refractoriness was analyzed. RESULTS: The percent of CD14(+) HLA-DR(low/-) monocytes was significantly higher in the lymphoma patients than in the healthy controls (control, 9.3 ± 4%; lymphoma, 35.8 ± 20.2%; P < 0.0001), higher in stage III& IV than stage II (stage II, 26.48 ± 17%, n = 26; stage III & IV, 50.8 ± 15.4%, n = 16; P < 0.0001), more in diffuse large cell lymphoma than other pathology types and in relapsed/refractory patients than in patients who achieved remission during follow-up (relapsed/refractory, n = 18, 45.7 ± 16.7%; remission, n = 16, 21.4 ± 16.2%; P < 0.0001). The arginase I level correlated with increased percent of CD14(+) HLA-DR(low/-) monocytes (P < 0.0001). CONCLUSION: Increased CD14(+) monocytes with loss of HLA expression were seen in patients with higher stage disease, more aggressive pathology, and in relapse or refractoriness to treatment. Identifying therapeutic strategies to overcome the suppressive properties of these monocytes could be of value.