The Effects Of Imatinib Mesylate On Foxp3~+ Regulatory T Cells And Their Subtypes In The PBL Of Patients With Gastrointestinal Stromal Tumor

Objective:To investigate the effects of imatinib mesylate on Foxp3~+Treg cells and their subtypes in the peripheral blood lymphocyte(PBL)of patients with gastrointestinal stromal tumor(GIST).Methods:66 GIST patients in the gastrointestinal surgery department of the Affiliated Hospital of Southwestern Medical University from January 2017 to January 2018 were enrolled according to our protocol and 31 healthy volunteers were recruited.The patients were divided into untreated GIST cases,target-treated GIST cases and healthy control group.The expression of Foxp3 mRNA in PBLs was detected by qRT-PCR and the ratio of Foxp3~+Treg cells and their three subtypes were measured via multicolor flow cytometry.The results of GIST patients would be compared with that of healthy volunteers.Foxp3~+Treg cells were separated into three subtypes:resting Treg cells,activated Treg cells and nonsuppressive Treg cells,basing on the expression of CD45RA and Foxp3.Statistical analysis was performed using the IBM Statistics SPSS 17.0 software package.Data were analyzed using analysis of variance,t-test,chi-square test,Fisher exact test,and other statistical methods.The difference was statistically significant when P<0.05 was defined,and when the three sets of data were compared in pairs,the test level was calibrated using Bonferroni.Graph Pad Prism 6.0 software was used to draw statistical charts.Results:A total of 66 patients with GIST and 31healthy volunteers were enrolled in this study,including 35 untreated patients,31target-treated GIST patients and 31 healthy control volunteers.The difference of average age and other general data between each two groups were not statistically significant(P>0.05).The results of qRT-PCR demonstrated that the Foxp3mRNA level in PBLs increased significantly in untreated GIST cases compared with healthy controls,and the Foxp3 mRNA level were lower in the target-treated group compared with the untreated group.The ratio of Foxp3~+Treg cells in the PBL of GIST patients,include untreated GISTs and target-treated GISTs was significantly higher than in the healthy donors(P<0.01).And the ratio of Foxp3~+Treg cells in the untreated GISTs was also higher than those patients accepted imatinib mesylate remedy(P<0.01).This difference also observed in the subtype of activated Treg cells showing that the ratio of activated Treg cells in the untreated GISTs was significantly higher than target-treated GIST cases(P<0.01),as well as the latter was higher than the healthy donors(P<0.01).Furthermore,we found that the ratio,both Foxp3~+Treg cells'and activated Treg cells',in the high-risk GISTs was obviously higher than low/intermediate risk patients(P<0.01),while there was no significantly difference between gender or tumor site in each trial group(P>0.05).Conclusions:1.Foxp3~+Treg cells increased in the PBL of patients with GIST than healthy donors,especially the aTreg subtype,and these changes may correlate with the disease progression.2.Imatinib mesylate may enhanced the anti-tumor immune response through suppressing the function of Foxp3~+Treg cells and their functional subtypes.