PD-1 high expression in T lymphocytes correlates with decreased survival in childhood B-cell precursor acute lymphoblastic leukemia

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common in pediatric malignancy. Despite high cure rates, relapse and treatment resistance remain major causes of mortality. Immune checkpoint molecules such as programmed death-1 (PD-1) have been implicated in T-cell dysfunction and immune evasion in cancer. In this study, we evaluated PD-1 expression on bone marrow CD4+ and CD8+ T lymphocytes from pediatric patients with BCP-ALL at diagnosis and investigated its association with clinical outcome. Flow cytometry analysis demonstrated significantly increased PD-1 expression, assessed as relative mean fluorescence intensity and as percentages of PD-1 low-density (PD-1LD) and high-density (PD-1HD) subsets, in patients compared with non-leukemic subjects. Survival analyses revealed that high frequencies of PD-1HD CD4+ and CD8+ T lymphocytes were significantly associated with inferior overall survival, whereas higher proportions of PD-1LD CD4+ T cells were associated with improved survival. Thus, our study identified two distinguishable T-cell populations in the bone marrow of pediatric patients with BCP-ALL: PD-1LD and PD-1HD. Furthermore, it demonstrated a correlation between high PD-1 expression on CD4 and CD8 T lymphocytes and survival in pediatric BCP-ALL. These results suggest that PD-1 may serve as a prognostic biomarker and a potential target for immune-based therapeutic strategies in BCP-ALL.