Higher Tim-3 Expression Concurrent with PD-1 in Exhausted CD4+ and CD8+T Cells in Patients with Acute Myeloid Leukemia

T cell dysfunctionality is a characteristic of patients with leukemia and plays an important role in leukemia progression. Increasing data showed immune checkpoint which mediate suppression and exhaustion of T cells play the crucial role in tumor immunosuppression. Upregulating Tim-3 and PD-1 could be identified on exhausted T cell in mice with acute myeloid leukemia (AML). Our previous study also showed co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with AML, and found a particular influence on CD8+T cells.In this study,we further investigated the characteristics of the distribution of TIM,and the co-expression with PD-1, CD244, and CD57 on CD3+, CD4+ and CD8+ T cells from patients with de novo AML and AML in complete remission (CR). Surface expression of PD-1, TIM-3 and CD244 and CD57 on CD3+, CD4+ and CD8+ T cells from peripheral blood samples from 18 newly diagnosed and 10 cases with AML-CR was analyzed by flow cytometry. 16 healthy individuals served as control. Significantly higher percentages of TIM-3+CD3+, TIM-3+CD4+T cells were found in AML group compared with healthy controls. Moreover, higher numbers of TIM-3+CD244+,TIM-3+CD57+CD4+T cells were identified in AML group, increased levels of TIM-3+CD8+, TIM-3+CD244+, TIM-3+CD57+CD8+T cells were also found in AML group, however, the difference was not statistical significant. Interesting, when we analyzed the coexpression of TIM-3 and PD-1 on CD4+ and CD8+ T cells, significant higher levels of TIM-3+PD-1+CD4+ and TIM-3+PD-1+CD8+T cells were identified either in de novo AML or AML-CR groups. Among the AML patients, one AML-M2 case with poor outcome, who had bladder tumor and underwent partial cystectomy and chemotherapy in 7 years ago, showed highest TIM-3 expression in almost T cell subsets. In conclusion, we characterized for the first time major T cell defects, including co-expression of TIM-3, PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML and found that TIM-3 may particular influence on CD4+T cells, while immunesupression with TIM-3 and PD-1 coexpression may involve on both CD4+ and CD8+ T cells, suggesting a poor anti-leukemia immune response in these patients.