The Expression And Mechanism Of Tim3in Patients With Acute Myeloid Leukemia

Objective: To investigate the expression and the role of Tim3on T cells,myeloid-derived suppressor cells (MDSCs) and CD11c+dendritic cells(CD11c+DCs) ofperipheral blood in patients with acute myeloid leukemia(AML). Consistently discuss theclinical significance of Tim3expression on these cells and the mechanism ofTim3-mediated immune escape.Methods: Collected clinical data of36patients who had been diagnosed with AMLby bone marrow MICM classification, and then gathered their heparin anticoagulationperipheral blood before any treatment. The heparin anticoagulation peripheral blood from20healthy volunteers was gathered as normal control. We used the methods of immunefluorescence labeling and flow cytometry to detect expression of Tim3on T cells, MDSCs,CD11c+DCs, respectively. Then discuss the clinical significance of Tim3expression on Tcells. Lastly detected co-expression of Tim3and PD-1on T cells, consistently with IFN-γsecreting level on T cells.Results:1.The proportions of CD4+T cells and CD8+T cells on lymphocytes in AMLpatients were (15.28±10.99)%and (9.19±7.54)%respectively, which were significantlylower than the proportion of normal controls [(31.12±2.22)%and (21.59±4.22)%respectively](P<0.05).2.The levels of Tim3expression on CD4+T cells and CD8+T cellsin AML patients were (4.77±3.560)%and (5.90±4.91)%respectively, which weresignificantly higher than the levels of normal controls [(0.73±0.62)%and (0.96±0.54)%respectively](P<0.05).3.The level of Tim3expression on CD4+T cells in AML patientswas significantly related with the presence of FLT3-ITD (P<0.05). The level of Tim3expression on CD8+T cells in AML patients was significantly related with the the NCCNrisk stratification (P<0.05).The ratio of CD4+T cells and CD8+T cells (CD4/CD8) in AMLpatients was also significantly related with the the NCCN risk stratification (P<0.05).4.Tim3and PD-1were co-expression on CD4+T cells and CD8+T cells in AML patients. 5.The IFN-γ secreting level in Tim3+CD8+T cells was significantly decreased thanTim3-CD8+T cells (P<0.05).6.The percentage of MDSCs in AML patients’ peripheralblood was (4.12±0.69)%,which was significantly higher than normal controls[(0.74±0.09)%](P<0.05).7.Tim3was higher expressed on MDSCs in AML patients thanin normal controls.8.The level of Tim3expression on CD11c+DCs in AML patients was(41.10±20.65)%,which was significantly higher than normal controls[(14.76±7.04)%](P<0.05).Conclusion:1.The high expression of Tim3on peripheral blood T cells in AMLpatients mediate T cell exhaustion/dysfunction and promote the proliferation of MDSCs,which can be an important mechanism of immune escape in leukemia.2.Furtherinvestigations are needed to explore the role of high expression of Tim3on CD11c+DCs.3.Tim3expression on AML patients’ immune cells was significantly related with the riskstratification and the poor prognosis, which reveal that Tim3is correlated with process ofAML, thus probably making Tim3become another new immunotherapy target.