Expression of the inhibitory checkpoints LAG-3, TIM-3, and PD-1 in NK cells and T cells in acute myeloid leukemia: preserved expression of LAG-3 is associated with patient survival.

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Despite advances in treatment, the average survival rate after diagnosis is low. AML also alters the patient's immune response further contributing to disease progression. The aim of this study was to analyze the expression of LAG-3, TIM-3 and PD-1 inhibitory checkpoints on NK cells and T cells from newly diagnosed AML patients and its impact in patient survival. NK cells and T cells from AML patients showed a lower expression of TIM-3 compared with healthy donors, whereas no significant differences were observed in the expression of LAG-3. The percentages of cells co-expressing these receptors showed a decrease in the percentage of LAG-3 + TIM-3 + PD-1 - NK and T cells from AML patients in comparison with healthy donors. Remarkably, the survival analysis of AML patients according to the expression of these receptors showed that higher expression of LAG-3 on NK cells and T cells was associated with better survival. In addition, those AML patients showing higher co-expression of LAG-3 and TIM-3 on NK and T cells had better survival (higher than 6 months) than those with lower co-expression of LAG-3 and TIM-3, therefore supporting that the expansion of NK and T cells with lower expression of these checkpoint receptors reflects a dysfunctional state associated with poor prognosis. This study identifies the expression of LAG-3 and TIM-3 checkpoints on NK and T cells as potential biomarkers of AML prognosis, contributing to define those patients that could benefit from checkpoint blockade therapies.