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根据疾病阶段和 TKI 药物,慢性髓性白血病患者 CD8+ T 细胞上 PD-1 表达的差异。

Differences in PD-1 expression on CD8+ T-cells in chronic myeloid leukemia patients according to disease phase and TKI medication.

机构信息

Department of Laboratory Medicine, Kyung Hee University School of Medicine, Kyung Hee University Hospital At Gangdong, Seoul, Korea.

Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

出版信息

Cancer Immunol Immunother. 2020 Nov;69(11):2223-2232. doi: 10.1007/s00262-020-02617-5. Epub 2020 May 30.

Abstract

Malignant cells can increase in number using immune escape mechanisms such as immune checkpoints. In this study, we evaluated the expression of an immune checkpoint programmed death 1 (PD-1) on T-cell subsets in chronic myeloid leukemia (CML). We obtained bone marrow aspirate samples from CML patients and from individuals without evidence of hematologic malignancies (controls). PD-1 expression on T-cell subsets was measured using flow cytometric analysis. PD-1 expression levels on CD8+ T-cells were significantly lower in complete hematologic response (CHR) than in controls, chronic phase, and blast phase (BP). In CML patients receiving imatinib and dasatinib, PD-1 expression levels on CD8+ T-cells were lower than that at diagnosis. PD-1 expression levels on CD8+ T-cells were positively correlated with quantitative levels of the BCR/ABL fusion gene. PD-1 expression levels on CD4+ T-cells were higher in BP than in CHR. PD-1 expression levels on CD4+ T-cells did not differ significantly according to different medications or quantitative BCR/ABL1 fusion gene levels. Low PD-1 expression on CD8+ T-cells might play a role in maintaining CHR in CML patients. Immune monitoring of PD-1 expression on CD8+ T-cells may predict the disease course. In cases of refractory disease or resistance to imatinib or dasatinib, the use of PD-1 inhibitors would be helpful.

摘要

恶性细胞可以通过免疫逃逸机制(如免疫检查点)增加数量。在这项研究中,我们评估了慢性髓系白血病(CML)中 T 细胞亚群上的免疫检查点程序性死亡 1(PD-1)的表达。我们从 CML 患者和没有血液恶性肿瘤证据的个体(对照)中获得了骨髓抽吸样本。使用流式细胞术分析测量 T 细胞亚群上的 PD-1 表达。在完全血液学缓解(CHR)中,CD8+T 细胞上的 PD-1 表达水平明显低于对照组、慢性期和急变期(BP)。在接受伊马替尼和达沙替尼治疗的 CML 患者中,CD8+T 细胞上的 PD-1 表达水平低于诊断时。CD8+T 细胞上的 PD-1 表达水平与 BCR/ABL 融合基因的定量水平呈正相关。BP 中 CD4+T 细胞上的 PD-1 表达水平高于 CHR。根据不同的药物或定量 BCR/ABL1 融合基因水平,CD4+T 细胞上的 PD-1 表达水平没有显著差异。CD8+T 细胞上低水平的 PD-1 表达可能在维持 CML 患者的 CHR 中发挥作用。对 CD8+T 细胞上 PD-1 表达的免疫监测可能预测疾病过程。在难治性疾病或对伊马替尼或达沙替尼耐药的情况下,使用 PD-1 抑制剂可能会有所帮助。

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