The Expression and Mechanism of Tim3 and PD-1 in Patients with Acute Myeloid Leukemia

Objective: To investigatethe expression and the role of Tim3 and PD-1 on T cells of peripheral blood in patients with acute myeloid leukemia(AML). Consistently discuss the clinical significance of Tim3 and PD-1 co-expression on these cells and the mechanism of Tim3-mediated immune escape.

Methods: Collectedclinical data of 36 patients who had been diagnosed with AML by bone marrow MICM classification, and then gathered their heparin anticoagulation peripheral blood before any treatment. The heparin anticoagulation peripheral blood from 20 healthy volunteers was gathered as normal control. We used the methods of immune fluorescence labeling and flow cytometry to detect expression of Tim3 on T cells. Then detected co-expression of Tim3 and PD-1 on T cells, consistently with IFN-γ secreting level on T cells.

Results: 1.The proportions of CD4⁺ T cells and CD8⁺ T cells on lymphocytes in AML patients were (15.28±10.99)% and (9.19±7.54)% respectively, which were significantly lower than the proportion of normal controls [(31.12±2.22)% and (21.59±4.22)% respectively] (P<0.05). 2.The levels of Tim3 expression on CD4⁺ T cells and CD8⁺ T cells in AML patients were (4.77±3.560)% and (5.90±4.91)% respectively, which were significantly higher than the levels of normal controls [(0.73±0.62)% and (0.96±0.54)% respectively] (P<0.05). 3.Tim3 and PD-1 were co-expression on CD4⁺ T cells and CD8⁺ T cells in AML patients. 4.The IFN-γ secreting level in Tim3⁺ CD8⁺ T cells was significantly decreased than Tim3^- CD8⁺ T cells (P<0.05).

Conclusion: 1.The high expression of Tim3 on peripheral blood T cells in AML patients mediate T cell exhaustion/dysfunction, which can be an important mechanism of immune escape in leukemia. 2.PD-1 and Tim3 co-expression On CD4⁺ T cells and CD8⁺ T cells in AML patients which were dificient in there ability to produce IFN-γ. Further investigations are needed to explore the correlation of co-expression PD1 and Tim3 with process of AML, thus probably making Tim3 become another new immunotherapy target.