Study On The Effect Of Decitabine On The Proportions Of Tregs In Peripheral Blood And Bone Marrow Of Patients With MDS/AML

Background:Myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML)are malignant clonal diseases of hematopoietic stem cells.Immune system abnormalities have been shown to play a critical role in the development of both of the diseases as a pathogenesis.Lately intervention for tumor immune regulation is the budding new trend in cancer treatment.Regulatory T cells(Tregs)have been proposed as good candidates to inhibit the body's anti-tumor immunity leading to the immune escape of tumor cells and causing the occurrence and development of diseases.The decitabine(DAC),as a DNA methyltransferase inhibitor,has immunomodulatory functions in addition to demethylation in the treatment of these two diseases.In this study,we evaluated the proportions of regulatory T cells in the peripheral blood and bone marrow of AML and MDS patients,and the correlation with the treatment of decitabines was analyzed,as well as clinical efficacy.Some valuable information may be provided to improve the treatment effect of AML and MDS,particularly by enhancing the body's anti-tumor immunity with DAC.Methods:64 AML and MDS patients(newly diagnosed?treated with decitabines or other chemotherapy regimens)were enrolled in our study along with 14 healthy individual.The proportions of the Tregs were analyzed by flow cytometry.Results:In peripheral blood:1.In the newly diagnosed MDS and AML patients,the proportions of Tregs was higher than the control group(P=0.05).2.The proportions of Tregs was significantly higher in the newly diagnosed AML patients than in the control group(P=0.002).3.There was no significant difference in the proportions of Tregs between the newly diagnosed MDS group and the newly diagnosed AML patients(P=1.00).4.The proportions of Tregs in patients with MDS and AML treated with DAC was significantly lower than that in the newly diagnosed group(P=0.009),and lower than that in other treatment groups(P=0.007);There were no statistical differences of Tregs between newly diagnosed and treated with other regimens(P=1.000).5.There was no difference in disease remission with DAC and other regimens(p=0.169).6.The proportions of Tregs in patients with AML treated with DAC was significantly lower than that of the newly diagnosed group(P=0.004),and was also significantly lower than that of the non-DAC chemotherapy group(P=0.023);There was no significant difference of Tregs's proportions in the newly diagnosed AML and non-DAC chemotherapy groups(P=0.351);7.In patients with MDS and AML treated with DAC,Tregs levels were significantly lower in the remission group than in the non-remission group(P=0.019).8.In patients with MDS and AML,Tregs in the 1-course DAC group were lower than those in the 1-course non-DAC chemotherapy group(P=0.016).9.In patients with MDS and AML,there was no difference in disease remission with 1 course of DAC and 1 course of other regimens(p=0.141).10.There was no difference in the proportions of Tregs in peripheral blood between the DAC and the control group in the MDS and AML or MDS or in the AML(P=0.974,P=0.702,P=0.977).In the bone marrow:1.In the newly diagnosed MDS and AML patients,the proportions of Tregs was significantly higher than the control group(P=0.043).2.In the newly diagnosed AML patients,the proportions of Tregs was significantly higher than that of the control group(P=0.029).3.The proportions of bone marrow Tregs in patients with MDS and AML treated with DAC was significantly lower than that in the non-DAC chemotherapy group(P=0.007).4.Tregs in the patient with DAC,remission group were lower than those in the non-remission group(P=0.050).5.There was no difference in the proportions of Tregs in the bone marrow between the DAC and the control group in the MDS and AML or MDS or in the AML(P=P=1.000,P=0.0.670,P=0.837).6.There was a significant correlation between the proportions of bone marrow Tregs and peripheral blood Tregs(P=0.000),and the correlation coeff icient was 0.595.Conclusions:The increased Tregs may involve in the inhibition of body's anti-tumor immunity.And the treatment of DAC can decrease the proportions of them and may delay the progression of the disease in AML and MDS patients through enhance the body's recognition of tumor cells and the immune function of killing them.There is a positive correlation between Tregs in the bone marrow and in peripheral blood.Thus,immunosuppression may occurs through direct contact in the tumor microenvironment of bone marrow in patients with AML and MDS.In summary,decitabine can achieve anti-tumor effects through well-known demethylation and cytotoxicity,and may also activate the body's immune effect on tumor cells by regulating tumor immunity and achieving anti-tumor effects in AML and MDS's patients.