The Relationship Between CD4~+CD25~+T Regulatory Cells And Prognosis Of Esophagus Cancer

Malignant tumor does harm to the health of human.Tumor therapy maily depends on operation,chemotherapy,radiotherapy.Nowadays,tumor immunotherapy will be developed into a new treatment model.The happening and the developing of tumor have close relationship with immunologic surveillance function.It has been found that there is a kind of unique T cell subgroup-CD4~+CD25~+T regulatory cell,which can control self-immune reaction and result in immune tolerance.This kind of cell subgroup possess the characteristic of immune suppression and immune disability,which hasn't restriction of MHC in immunosuppressive action.This experiment will explore the mechanism of CD4~+CD25~+ regulatory T cell acting on esophagus cancer.By detecting the distribution of CD4~+CD25~+ regulatory T cell,we will demonstrate the mechanism of CD4~+CD25~+ regulatory T cell.The purpose is to provide a new way for esophagus cancer treatment.PartⅠThe detection and significance of CD4~+CD25~+ regulatory T cell of esophagus cancer patientsOBJECTIVEBy detecting the distribution of CD4~+CD25~+ regulatory T cell,This experiment will explore the mechanism of CD4~+CD25~+ regulatory T cell acting on esophagus cancer and demonstrate the mechanism of CD4~+CD25~+ regulatory T cell.The purpose is to provide a new way for esophagus cancer treatment.METHODSCD4~+CD25~+regulatory T cells in the peripheral blood and resected tissue of esophagus cancer patients were evaluated with the flow cytometry for lymphocyte. Peripheral blood mononuclear cells(PBMCs) coming from 37 patients and 25 healthy controls separated by centrifugation over the liquid of ficoll-hypaque,20 case freshly resected esophagus cancer samples were dealed with the method of enzymatic digestion, tumor-infiltrating lymphocytes were isolated.After stained with anti,all samples were evaluated with the flow cytometry by gating on lymphocytes and CD4~+CD25~+ regulatory T cells were detected their proportion,we expect to find out the relationship between the proportion of CD4~+CD25~+ regulatory T cells and clinical pathological information.RESULTS1.The proportion of CD4~+CD25~+ regulatory T cells in the peripheral blood of 37 esophagus cancer patients was(12.31±3.58)%,the proportion of CD4~+CD25~+ regulatory T cells of 20 case resected esophagus cancer samples was(13.81±2.68)%.The above both were obviously higher than those of healthy controls(5.92±1.66)%,there both have statistical significance(P＜0.01).2.32 cases of squamous carcinoma patients,5 cases of adenocarcinoma patients,the proportion of CD4~+CD25~+ regulatory T cells in the peripheral blood mononuclear cells were(12.55±3.70)%,(10.76±2.35)%respectively,which were obviously higher than those of healthy controls(P＜0.01),but there wasn't obviously discrepancy among different pathological types(P＞0.05).3.The proportion of CD4~+CD25~+ regulatory T cells in the peripheral blood of esophagus cancer patients withⅠ,Ⅱ,Ⅲstage was respectively(11.10±2.56)%,(12.55±3.67)%,(14.32±3.85)%.There was statistical significance(P＜0.01).That is to say the proportion of CD4~+CD25~+ regulatory T cells in late stage was higher than that in early stage.4.The proportion of CD4~+CD25~+ regulatory T cells in the peripheral blood of esophagus cancer patients with lymphonode metastasis is(13.44±3.72)%,was significantly higher than those without lymphonode metastasis(10.83±2.85)% (P＜0.05).5.There weren't statistical significance between the proportion of CD4~+CD25~+ regulatory T cells in the peripheral blood of esophagus cancer patients with different age,sex,tumor location,depth of tumor infiltration,pathological grades (p＞0.05).CONCLUSIONThe relative increase in CD4~+CD25~+ regulatory T cells in the peripheral blood may be related to immunosuppression and tumor progression in patients with esophagus cancer.The finding suggests that CD4~+CD25~+ regulatory T cells in peripheral blood may be significant for prognosis analysis of esophagus cancer patients.PartⅡThe relationship between CD4~+CD25~+ regulatory T cell and survival rate in esophagus cancer patients after the operationOBJECTIVEBy detecting FOXP3 in esophagus tumor tissue,this experiment is to explore the relationship between expression of FOXP3 and survival rate,and to predict the effect of CD4~+CD25~+ regulatory T cell on prognosis of esophagus cancer patients indirectly.METHODFOXP3(the specific surface marker of CD4~+CD25~+regulatory T cells) expression was detected in 60 esophagus cancer patients by immunohistochemical technique.Survival curves were plotted according to the Kaplan-Meier estimates.It is to compare the different survival rates between the two kinds of patients with overexpression and without overexpression of FOXP3.RESULTS1.Of 60 esophagus cancer patients with surgically treated by immunohistochemical technique,the cases of overexpression and without overexpression of FOXP3 were 29 and 31 patients respectively.The overexpression ratio of FOXP3 was 48.33%.Its overexpression was not related to tumor types,pathological grades,sex,age and so on (p＞0.05).2.The overexpression of FOXP3 in cancer tissues were related to clinical stages and lymph node metathesis status.The prognosis of patients with FOXP3 overexpression was worse than that of the patients without overexpression of FOXP3.The 5-year survival rate of overexpression and without overexpression of FOXP3 were 10.34%,22.58% respectively,there was statistical significance(P＜0.05).Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher ratio of CD4~+CD25~+regulatory T cells in the peripheral blood was worse.CONCLUSIONCD4~+CD25~+T regulatory cells are presumed to have reference to prognosis of the esophagus cancer patients through the immunohistochemical technique and the analysis of clinical information.The use of depletion of CD4~+CD25~+ regulatory T cells to treat esophagus cancer patients may be an effective strategy.It is worthwhile to make an intensive study to see whether CD4~+CD25~+regulatory T cells could be an independent prognostic indicator.