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The Imbalance Of Th1/Th2and Th17/Treg In Patients With Uterine Cervical Cancer And The Changes Of TheCD4+Cells After Surgery

Posted on:2015-06-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:F YuanFull Text:PDF
GTID:1224330467961142Subject:Obstetrics and gynecology
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PART I The imbalance of Th1/Th2and Th17/Treg in patients with uterine cervical cancerBackground:Thl/Th2and Th17/Treg were reported to play critical roles in immunoregulation, and their imbalance may lead to autoimmune diseases and allergic reactions. To test the proportions and cytokines level changes of Thl/Th2and Th17/Treg cells in peripheral blood of uterine cervical cancer cervical intraepithelial neoplasia (CIN) and HR-HPV(+) women without cervical dysplasia was important for understanding the relationship between CD4+T cells subsets or immune functional status in patients。Methods:We examined the expression of IFN-γ、IL-4、IL-17and Foxp3in uterine cervical cancer (UCC) patients, cervical intraepithelial neoplasia (CIN) patients, HR-HPV(+) women without cervical dysplasia and healthy controls by flow cytometry.IFN-γ-producing CD4+cells as Thl cells, Interleukin (IL)-4-producing CD4+as Th2cells, Interleukin (IL)-17-producing CD4+cells as Th17cells, CD4+CD25+Foxp3+T cells as Treg cells were expressed as a percentage of the total CD4+cells.We examined the expression of IFN-γ、IL-4、IL-17and Foxp3by immunohistochemistly in uterine cervical cancer (UCC) patients, cervical intraepithelial neoplasia (CIN)Ⅲ patients and healthy controls. The concentrations of plasma IFN-γ、IL-4、IL-17、IL-10、 IL-23and TGF-β were measured by ELISA.Results:1.Compared with healthy controls, patients with UCC or CIN had a higher proportion of Th2、Th17and Treg cells, but had a lower Th1cells (P<0.05)。 Notably, in UCC patients, the increased Th2cells and Th17cells prevalence were associated with clinical stage, lymph node metastases and vasoin, while the elevated Th2、Th17and Treg cells frequency and decreased Th1cells were also associated with tumor size (P<0.001). Furthermore, the ratio of Thl/Th2and Th17/Treg were significantly higher than that in UCC or CIN patients respectively.The significant change in HPV(+) women was not found in Th1,Th2,Th17or Treg.2.The expression of IL-4in cervical tissues was significantly higher and the expression of IFN-γwas significantly lower in UCC and CIN patients(P<0.01). The expression of IL-17and Foxp3were significantly higher only in UCC(P<0.05) but not in CIN patients compared with controls3. The plasma levels of IL-4、IL-17、IL-10、IL-23and TGF-β were significantly higher in UCC patients than those in healthy controls and CIN patients. Only the plasma level of IFN-ywas significantly lower in UCC patients and CIN patients Conclusions:(1) There are imblance of Thl/Th2and Th17/Treg cells in UCC and CIN patients.(2)In the peripheral blood, the lower Thl cells and the higher Th2, Th17and Treg cells in the UCC and CIN patients, there is a immune balance in HPV (+) women.(3)Thl/Th2and Th17/Treg imbalance involved in the occurrence and development of rvical cancer. PART Ⅱ The changes of the CD4+cells in patients with UCC or CIN after surgeryObjective:To study the pre-and postoperative change of Th1, Th2,Thl7cells and Treg cells subsets on the cellular immune function in peripheral blood of patients with UCC and CINMethods:The levels of peripheral blood CD4+cell subsets were examined in20patients with UCC and21CIN patients on3days before operation1month and6month after operation by flow cytometric analysis.Results:1) The change of Thl cells:After operation, the levels of Thl were higher than that in preoperative, and up to the level of health control1month later.6months later, the normal level was remained both in UCC and CIN patients.. There are same information in Th17cells and Treg cells in CIN patients.2) The change of Th2cells:The levels of Th2in postoperative group were significantly lower than that in preoperative and1month later in CIN patients, but in UCC patients, the levels of Th2was down to the level of health control until6months later(P<0.05). There are same information in Th17cells and Treg cells in UCC patients.3) For4patients with lymph node metastases and vasoin, after radiochemotherapy, the immune balance was improved until6months。Conclusion:1)These data suggested that Patients with UCC or CIN had immunity disorder before operation.2) Operation could free them from immunosuppression...
Keywords/Search Tags:Uterine cervical cancer, Cervical intraepithelial neoplasia, Th1/Th2, Th17/Treg, cytokine, immune imblance
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