You Eunkyoung, Park Chan-Jeoung, Cho Young-Uk, Jang Seongsoo, Lee Min Young, Kim Hery, Koh Kyung Nam, Im Ho Joon, Choi Eun-Ji, Lee Je-Hwan, Lee Kyoo-Hyung
Department of Laboratory Medicine, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea.
Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Ann Clin Biochem. 2024 Mar;61(2):79-89. doi: 10.1177/00045632231184716. Epub 2023 Nov 21.
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.
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.
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 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.
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.
免疫检查点参与肿瘤逃避免疫系统的机制。我们的目的是评估急性髓系白血病(AML)患者,以根据诊断和治疗确定检查点分子的表达水平,并确定检查点阻断的最佳候选者。
从279例处于不同疾病状态的AML患者和23名对照者中获取骨髓(BM)样本。对PD-1和PD-L1/PD-L2表达进行流式细胞术分析。
与对照相比,AML诊断时CD8 T细胞上的程序性死亡-1(PD-1)表达水平升高。继发性AML诊断时白血病细胞上的PD-L1和PD-L2表达水平显著高于AML。异基因造血干细胞移植(allo-SCT)后CD8和CD4 T细胞上的PD-1水平显著高于诊断时和化疗(CTx)后。急性移植物抗宿主病(GVHD)组CD8 T细胞上的PD-1表达高于非GVHD组。CD8 T细胞上PD-1高表达患者的总生存期显著短于PD-1低表达患者。
总之,接受allo-SCT的患者表现出高PD-1表达,提示allo-SCT增加T细胞上的PD-1表达,allo-SCT后CD8 T细胞上PD-1高表达的患者预后较差。对于这些患者,PD-1阻断可能是一种免疫治疗策略。