Increased PD-1 expression of bone marrow T-cells in acute myeloid leukaemia patients after stem cell transplantation, and its association with overall survival.

Abstract

Background: Immune checkpoints are involved in mechanisms by which tumours escape from the host immune system. Our aim was to evaluate acute myeloid leukaemia (AML) patients to determine expression levels of checkpoint molecules according to diagnosis and treatments, and to identify optimal candidates for checkpoint blockade.

Methods: Bone marrow (BM) samples were obtained from 279 AML patients at different disease status and from 23 controls. Flow cytometric analyses of PD-1 and PD-L1/PD-L2 expression were performed.

Results: Programmed death-1 (PD-1) expression levels on CD8⁺ T-cells at AML diagnosis were increased compared to controls. PD-L1 and PD-L2 expression levels on leukaemic cells at diagnosis were significantly higher in secondary AML than in de novo AML. PD-1 levels on CD8⁺ and CD4⁺ T-cells after allo-SCT were significantly higher than those at diagnosis and after CTx. PD-1 expression on CD8⁺ T-cells increased in the acute GVHD group than in the non-GVHD group. The overall survival of patients with high PD-1 expression on CD8⁺ T-cells was significantly shorter than that of patients with low PD-1 expression.

Conclusions: In conclusion, patients who underwent allo-SCT exhibited high PD-1 expression, suggesting that allo-SCT increases PD-1 expression on T-cells, and the patients with high PD-1 expression on CD8⁺ T-cells after allo-SCT showed the poor prognosis. For these patients, PD-1 blockade could be an immunotherapeutic strategy.