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Study The Relationship Of Cd4~+cd25~+foxp3~+ Regulatory T Cells And The Clinical Stage And Chemotherapy Of Lung Cancer

Posted on:2010-05-09Degree:MasterType:Thesis
Country:ChinaCandidate:Y P WangFull Text:PDF
GTID:2194360302477171Subject:Oncology
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Background and objectives:Recent study found a class T-cell,saying that regulatory T cells(Treg cell, referred to as Treg),who has a unique regulatory function and plays an important role in the maintenance of immune homeostasis and regulating the immune response. Recently,extensive attention by the people,become one of the hot-disciplinary research for it is closely related to the occurrence of autoimmune diseases and immune suppression of cancer.At present,More Studied in the subtypes of CD4~+CD25~+Foxp3~+Treg,which was one class of immunoregulatory function of T cell subsets.And Foxp3 protein is an important transcription factor that expressed in Treg cells specifically,which control its differentiation and development,but also their specific markers.Because it is more mature in the study of CD4~+ CD25~+ Foxp3~+ regulatory T cells than others,and in this article refers specifically Treg cells to CD4~+CD25~+Foxp3~+Treg cells.Since Sakaguchi et al propose the concept firstly of CD4~+ CD25~+ Treg cell in 1995,more and more research and found confirmed that regulatory T cells play an important role in physiological and pathological conditions of immune regulation.Especially in pathological cases,it is closely related to the occurrence of autoimmune diseases and immune suppression of cancer,studies found that tumor cells can produce a series of mechanisms to escape anti-tumor immune response;On the other hand,normal T cells contain CD4~+CD25~+Foxp3~+ regulatory cells,which mediated immune tolerance likely to affect the immune system response to tumor antigens,thus to affect the occurrence and development of tumors. A number of studies have found the relationship between a tumor and Treg cells.The proportion of Treg was significantly increased,FOXP3 expression of the phenomenon in the peripheral blood lymphocytes and tumor-infiltrating lymphocytes of,cancer patients such as stomach cancer,esophagus cancer,liver cancer,pancreatic cancer, breast cancer patients etc,which enhances the body's tolerance for the tumor antigen and inhibit the body create an effective anti-tumor immune response to remain patients with low immune function,and all that has played an important role in the emerge and development process of tumor.Malignant tumor threaten seriously life and health of human,lung cancer is the most common primary malignant tumor of the lung,the last 50 years the incidence and mortality of lung cancer are rising rapidly in the world,especially in developed industrial countries,patients with lung cancer have been on top of the list in male patients who died of cancer.At present,the incidence of lung cancer is the highest in the world's cancer,also the one of refractory tumors in China.Tumor occurrence, development and prognosis are closely related to immune function.Studies have shown that the proportion of Treg cells significantly increased,FOXP3 expression in peripheral blood and tumor tissue of tumor-bearing mice,which enhances the body's tolerance to the tumor antigen,further study Treg cells play immunosuppressive effects mainly through cell-cell intercontact and secretion of inhibitory cytokines to suppress the body create an effective anti-tumor immune response and to suppress autoreactive T cells and helper T cell activation,namely,to inhibit the function of CD4~+ and CD8~+ T cells so that patients with tumor are in low immune function,and all that lead malignant transformation cells to escape immune surveillance,and played an important role in the development process of tumor incidence.Radiotherapy and chemotherapy are commonly used in tumor treatment,but radiotherapy and chemotherapy on tumor cells not only have a killing effect,but also destruction of normal lymphocytes.And lymphocytes are the main immune cells of the body,as Treg cells suppress tumor immunity,so whether Treg cells is related to tumor chemotherapy deserves further study.Treg cell about lung cancer patients is currently less in clinical studies.The experimental will research for the relation of Treg cells and clinical stage and chemotherapy of lung cancer by detecting the changes of CD4~+CD25~+Foxp3~+regulatory T cells in peripheral blood in patients with lung cancer and to explore its clinical significance.Methods:1.Collect pathologically confirmed newly diagnosed 61 cases of lung cancer patients, 15 cases of normal volunteers as controls.2.Draw out 3ml peripheral venous blood of Samples of fasting patients with lung cancer before chemotherapy and after two cycles of chemotherapy(evaluation after two cycles of chemotherapy treatment),cryopreservation for standby.3.using fluorescent-labeled monoclonal antibody(FITC labeled mouse anti-human CD4~+,PE-Cy5 labeled mouse anti-human CD25~+,PE labeled mouse anti-human FOXP3~+) staining of samples after removing the red blood cells in blood cryopreservation.4.detecting the ratio for Treg cells in account of CD4~+ T cells by flow cytometry.5.process experimental data with SPSS13.0 software.Two samples are compared with t tests,more than 2 samples were found to compare with single-factor analysis of variance,a=0.05 for the difference statistically significant.Results1.the ratio of Treg cells accounted for CD4~+T cells in peripheral blood was significantly higher in patients with lung cancer(9.28±2.10)%than that in the control group(2.63±1.28)%,and the difference was statistically significant(P<0.01).2.the ratio of Treg cells was significantly higher inⅢ+Ⅳperiod(12.64±3.38)% than inⅠ+Ⅱperiod(6.84±2.19)%,and the difference was statistically significant(P<0.01).3.the outcome of patients undergoing chemotherapy:3.1 The cases of effective treatment(PR):the proportion of Treg cells after chemotherapy is lower than before chemotherapy(before chemotherapy:11.94±2.41, after chemotherapy:9.27±1.64),the difference was statistically significant(P<0.01).3.2 Cases of Stability and progress(SD+PD):the proportion of Treg cells after chemotherapy has increased than that before chemotherapy(before chemotherapy: 12.35±2.83,after chemotherapy:13.46±2.52),the difference was statistically significant(P<0.05).3.3 After chemotherapy the proportion of Treg cells significantly decreased in PR (9.27±2.64)%than in SD + PD(13.46±2.52)%,the difference was statistically significant(P<0.01).It show that effective chemotherapy(PR) the ratio of Treg cells decreased,but poor efficacy(SD+PD) the ratio further increase.Conclusion1.The proportion of Treg cells Treg in peripheral blood of patients with lung cancer is significantly higher than that in normal.and the higher stages,the more obvious increase in the ratio.2.Patients with chemotherapy:the ratio decreased significantly after chemotherapy than before chemotherapy in effective chemotherapy for patients,poor efficacy of chemotherapy the ratio was significantly higher after chemotherapy than before chemotherapy,and after the chemotherapy the ratio of Poor efficacy chemotherapy was significantly higher than that of effective cases.3.It can inference from the above that the changes of the proportion of Treg cells are related with the occurrence,development and prognosis of lung cancer.NOTE: We can provide a basis for early diagnosis of tumors,evaluation of efficacy and monitoring development and prognosis of tumor through the monitor for Treg cells in peripheral blood of patients.And provide new ideas for immunotherapy for lung cancer.
Keywords/Search Tags:lung cancer, CD4~+CD25~+Foxp3~+Treg, chemotherapy
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