RESUMO
Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells that show increased expression in cancer patients; however, the molecular mechanisms underlying their generation and function are unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer (BC), the presence and relevance of monocytic (Mo)-MDSCs are unknown. Here, we report for the first time increased chemokine and chemokine receptor production by Mo-MDSCs in BC patients. A clear population of Mo-MDSCs with the typical cell surface phenotype (human leukocyte antigen-antigen D related [HLA-DR]low/- CD11b+ CD33+ CD14+) increased significantly during disease progression. In addition, the chemokine receptor expression level on Mo-MDSCs in patients with invasive BC was the highest. Furthermore, different chemokine receptor expression patterns were noted in Mo-MDSCs between healthy controls (HC) and BC patients. Additionally, CD4 T cells proliferations were significantly decreased in the invasive BC groups compared with the HC group. However, the ductal carcinoma in situ (DCIS) group had no significantly compared with the HC group. Our data suggest that monitoring chemokine and chemokine receptor production by Mo-MDSCs may represent a novel and simple biomarker for assessing disease progression in BC patients.
RESUMO
PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b-CD314+CD3-CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.
RESUMO
Background: The study examined the difference in the expression of the receptor for activated C kinase 1 (RACK1) between anaesthesia with propofol and isoflurane in rats with myocardial ischemia-reperfusion injury (IRI). Methods: Male Sprague-Dawley rats were studied. Anaesthesia was induced with xylazine 20 µg/g by intraperitoneal injection and maintained with propofol or isoflurane. Myocardial IRI was induced by ligating the left anterior descending artery for 1 hour. Reactive oxygen species (ROS), cardiomyocyte apoptosis, the expression of RACK1 and toll-like receptor 4 (TLR4), and the heart injury score were compared between the two groups. Results: Cardiomyocyte apoptosis with ROS was significantly lower in the propofol group than in the isoflurane group. The propofol group had significantly higher RACK1 expression and lower TLR4 expression, compared with the isoflurane group (RACK1, 1970.50 ± 120.50 vs. 1350.20 ± 250.30, p<0.05; TLR4, 980.50 ± 110.75 vs. 1275.50 ± 75.35, p<0.05). However, the heart injury scores in the two groups did not differ significantly (3.56 ± 0.29 vs. 4.33 ± 0.23 in the propofol and isoflurane groups, respectively, p=0.33). Conclusion: There were significant differences in inflammation and apoptosis, including the expression of RACK1 and TLR4, after myocardial IRI between the propofol and isoflurane groups. However, both groups had similar heart injury scores.
