Regulation Of Treg Cell Expression Level Through STAT3 Signal Pathway By SOCS3 In Childhood Acute Lymphoblastic Leukemia

Objective Regulatory T(Treg)cells are a group of cells in T cell subsets that possess the immunity functions,which can control the effects of anti-tumor response,and the immune escape can exist in tumor cells under this kind of effects.In addition,Treg cells also play very important roles in the process of emergence and development of cancer.Leukemia is the most common malignant tumor in children,and the acute lymphoblastic leukemia(ALL)account for about 75%.Previous studies indicate that there are multiple abnormally activated signal pathways in in leukemia cells.Among these pathways,the continuous activation of JAK/STAT signal pathway is closely related to the occurrence and development of leukemia.In recent years,a group of JAK/STAT inhibitors have been discovered which are known as supressors of cytokine signalling(SOCS).By adjusting STAT3 activation,SOCS3 can affect the levels of Treg cells,and then the body’s anti-tumor immune status can be influenced.This research tries to measure the expression levels of Treg cells,STAT3 m RNA and SOCS3 m RNA in childhood acute lymphocytic leukemia,finds their connections and provides a new thought to the tumor immunotherapy of leukemia.Methods This research chose 45 accepted and standardized childhood ALL cases from Jan 2015 to Jan 2016,together with 13 normal children in the control group.These 45 standardized cases referred to those were in accordance with ALL diagnosis using morphology,immunology,cytogenetics,molecular biology,MICM.Meanwhile,the following cases were excluded,including the Mature B acute lymphoblastic leukemia,mixed acute lymphoblastic leukemia,immunodeficiency disease,second tumor and noninitial treatment acute lymphoblastic leukemia.This research measured the expression levels of STAT3 m RNA,SOCS3 m RNA and Treg cells in peripheral blood mononuclear cell of these 45 ALL cases and 13 control group cases.The fluorescent quantitative PCR method was used to test the expression levels of STAT3 m RNA and SOCS3 m RNA,and the expression levels of Treg cells were tested by the flow cytometric method both in ALL cases and normal control group cases.Variance analysis and rank sum test were adopted to compare the relationships between these expression levels of Treg cells,STAT3 m RNA and SOCS3 m RNA.Results 1.SOCS3 m RNA and STAT3 m RNA expression levels were different between the initially treated ALL cases and control group cases.The ALL cases had lower SOCS3 m RNA expression level(P<0.05)and higher STAT3 m RNA expression level(P<0.05).2.The test results of Treg cells showed that levels of Treg cells were higher in initially treated ALL cases than those in normal control groups(P<0.05).3.The STAT3 expression levels were positively correlated with the Treg cell levels(r=0.751,P<0.05),while SOCS3 expression level was negatively correlated with those of STAT3 and Treg cells(STAT3: r=-0.61,P <0.05;Treg: r=-0.558,P <0.05).Conclusion In childhood ALL cases,SOCS3 negatively regulates the expression levels of STAT3,and the low expression levels of SOCS3 can lead to continuous activation of STAT3,which results in the high expression levels of Treg cells.The regulation effects of SOCS3 on Treg cells provides new ideas to the treatment of leukemia.The regulation of SOCS3 expression may be used as a new tumor immunotherapy method for ALL.