The Study Of Th17and Foxp3~+Regulatory T Cells In Peripheral Blood In The Clinic Therapy Of Gastric Cancers

Objective:T lymphocytes play an important role in antitumor immunity. All kinds of immune cells keep certain ratio in the number in normal body.If the ratio is imbalanced,it will cause lower immune function or immune tolerance,and tumor cells will escape from the immune system from the host.So far it has been discovered that there are Thl,Th2,Treg and T helper cell17subsets in CD4+T cells.Treg cells are inhibitory cells in antitumor immunity,and they increase in the peripheral blood and tumor microenvironment in the colon cancer,breast cancer,ovarian cancer,lung cancer and pancreatic cancer.It is reported that the increasition of CD4+CD25+Foxp3+Treg and tumor progression are closely related.Newly discovered T helper cell17is an independent CD4+T cell subset,secreted characteristic cytokine IL-17,and plays important role in autoimmune disease,cancer,infectious diseases and transplant rejection.T helper cell17plays a complicated role in antitumor immunity.Researches show that T helper cell17and its related cytokine have both function in antitumor and promoting tumor.T helper cell17and Treg cells are mutually inhibited and antagonisted in the differentiation process and immune effection.It has been shown that the relationship between Treg and T helper cell17is similar to Th1/Th2balance,and it is dynamically.This study aims to evaluate immune condition of gastric cancer patients and levels of Treg cells and T helper cells17in different conditions include before and after radiotherapy,chemotherapy,biotherapy,and their relationship through detecting the number of Treg cells and T helper cells17and related cytokine in the peripheral blood,to provide some beneficial data for gastric cancer comprehensive therapy. Methods:Select65patients with gastric cancer not treated before,group them according to the AJCC standard,and test the proportions of T helper cells17and CD4+CD25+Foxp3+cells in peripheral blood by flow cytometry analyzer before treatment,then treat them according to the NCCN guidelines for gastric cancer,after treatment test again the proportions of T helper cells17and CD4CD25+Foxp3+Treg cells,and analyse the difference with different levels and clinical stages,finally analyse the influence of surgical therapy,radiotherapy,chemotherapy,biotherapy on the T cells and the relationship of the level and therapeutic effect.Choosing63healthy persons as control group,test the level of T helper cells17and CD4+CD25+Foxp3+Treg cells by flow cytometry analyzer,and test the expression level for related cytokine such as IL-17,IL-23,IL-6and TGF-betal using enzyme linked immunosorbent assay,and analyse the potential interrelationship of T helper cells17and Treg cells in peripheral blood and the clinical characteristics,including gender,age,the preoperative concentration of the diameter of the tumor,histologic type and TNM stages.Results:1. The CD4+CD25+Foxp3+Treg cells in peripheral blood with gastric cancer increased compared with normal control group,P<0.05,while T helper cells17decreased and the ratio of Treg:Th17increased.2. The level of Treg and T helper cell17was dynamically changed.3. The level of T helper cells17and Treg cells in peripheral blood in gastric cancer had positive correlation with their stage.The frequency of T helper cells17with advanced disease was significantly decreased compared to that in those with early disease,P<0.05,while the frequency of Treg with advanced disease was increased compared to that in those with early disease,P<0.05.The ratio of Treg/Th17in PBMCs in gastric cancer was higher than normal group,and it was significantly elevated in advanced compared to that in early disease.4. The multivariate linear regression analysis showed that there was no relationship between T helper cell17、Treg cells、the ratio of Treg:Th17in peripheral blood with gastric cancer and their gender,age,the preoperative concentration of the diameter, histological type(P>0.05),except the TNM stage(P<0.05).5. The level of Foxp3+Treg cells in peripheral blood in patients decreased after surgy and chemotherapy, while T helper cells17increased. The level change in Foxp3+Treg cells and T helper cells17in peripheral blood in patients before and after radiotherapy are not dramaticlly,P>0.05.6.The level of CD4+CD25+Foxp3+Treg cells in peripheral blood in patients decreased while T helper cells17increased after CIK biotherapy,and both the differences were significant,P<0.05.7. The expressions of TGF-β1and IL-6were higher in patients with gastric cancer than that in control groups(P<0.05),and increased in advanced group than that in early group(P<0.05),and they decreased after treatment(P<0.05).Meanwhile the expressions of IL-17and IL-23were lower in patients than control groups(P<0.05),and decreased in advanced group than early group(P<0.05),and they increased after treatment(P<0.05).Conclusion:1. The level of Treg cells in peripheral blood with gastric cancer elevated in disease and then gradually increased according to the disease progression.In contrast, the level of T helper cells17was lower in disease and then gradually decreased according to the disease progression.That indicates that the Treg cells and T helper cells17might participate in occurrence and progression in gastric cancer.2. The relationship between Treg and T helper cell17in peripheral blood with gastric cancer was unbalanced.3. The level of Foxp3+Treg cells in peripheral blood in patients decreased after surgery,chemotherapy and CIK biotherapy,while the level of T helper cells17increased after these treatments. Surgery,chemotherapy,CIK biotherapy can correct patients’ immune suppression condition.4. The level decreased in Foxp3+Treg cells and increased in T helper cells17in peripheral blood in patients after radiotherapy are not dramaticlly.5. CIK biotherapy.can corret the unbalance of Th17/Treg.We infer that regulation the balance of Th17/Treg in peripheral blood.in patients with gastric cancer may be one of the possible mechanism of CIK therapy.