The expression patterns and prognostic significance of PD-1 and TIM-3 on T cells and the differentiated subsets in acute myeloid leukemia.

Researches on the immune checkpoint molecule and its clinical application in acute myeloid leukemia (AML) fall behind solid tumors. The expression patterns and prognostic significance of immune checkpoint molecules across T cells and T-cell differentiated subsets in AML require further elucidation. In the present study, bone marrow (BM) samples from 165 newly diagnosed AML patients and 12 healthy donors (HDs) were tested PD-1 and TIM-3 expression on CD4 and CD8T cells as well as their differentiated subsets by multi-parameter flow cytometry. Compared with HDs, PD-1 was significantly overexpressed on total CD4T cells and their major constituent subsets (naïve, central memory, and effector memory T cells; all P < 0.05), whereas TIM-3 was overexpressed on both total CD4 and CD8T cells, as well as all differentiated subsets (all P < 0.05). Both high expressions of PD-1 on CD8T and TIM-3 on CD4T cells were associated with poor relapse-free survival (RFS) and event-free survival (EFS) (all P < 0.05). In addition, high PD-1 expression on CD8T cells independently predicted poorer RFS and EFS (P = 0.010 and 0.0011). Further stratification by T-cell subsets revealed that high PD-1 expression on naïve CD4T cells and TIM-3 on effector CD4T cells emerged as independent adverse prognostic factors for RFS (P = 0.018 and P = 0.034, respectively), replacing the prognostic impact of PD-1 on total CD8T cells. However, high PD-1 expression on CD8T cells remained the sole independent predictor of EFS (P = 0.0065). In conclusion, the expression patterns of PD-1 and TIM-3 in the BM T cells and their differentiated sub-populations in newly diagnosed AML patients were distinct from HDs, and predicted outcomes.