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

Abstract

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 CD8⁺T cells as well as their differentiated subsets by multi-parameter flow cytometry. Compared with HDs, PD-1 was significantly overexpressed on total CD4⁺T 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 CD8⁺T cells, as well as all differentiated subsets (all P < 0.05). Both high expressions of PD-1 on CD8⁺T and TIM-3 on CD4⁺T 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 CD8⁺T 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 CD4⁺T cells and TIM-3 on effector CD4⁺T 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 CD8⁺T cells. However, high PD-1 expression on CD8⁺T 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.