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新诊断急性髓系白血病白血病细胞及肿瘤微环境中 TIM-3 和 PD-1/PD-L1 表达的特征及临床相关性。

Characteristics and clinical correlation of TIM-3 and PD-1/PD-L1 expressions in leukemic cells and tumor microenvironment in newly diagnosed acute myeloid leukemia.

机构信息

Department of Medicine, Division of Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Research Unit in Translational Hematology, Chulalongkorn University, Bangkok, Thailand.

出版信息

Leuk Lymphoma. 2022 Feb;63(2):450-456. doi: 10.1080/10428194.2021.1984454. Epub 2021 Sep 29.

Abstract

Dual targeting of TIM-3 and PD-1/PD-L1 pathways is currently under investigation for cancer immunotherapy. The interaction of these immune checkpoints remains unclear in the leukemic microenvironment of acute myeloid leukemia (AML). We performed an immunophenotypic study of bone marrow in 37 newly diagnosed AML patients. High levels of TIM-3 expression on AML blasts were correlated with first 7 + 3 induction failure (CR 16.2% non-CR 36.4%,  = .038). In contrast, high TIM-3 levels on natural killer (NK) cells were associated with complete remission (CR) status after induction (CR 24.7% non-CR 6.5%,  = .035). Few PD-L1 positive AML blasts and PD-1 or PD-L1 positive NK cells were observed. Although the exhausted PD-1 expressing T cells were detected in 28.3% of T cells, the double positive of PD-1 and TIM-3 T cells were rarely detected. In summary, the TIM-3 levels on AML blasts and NK cells are potentially the prognostic biomarkers in AML.

摘要

双重靶向 TIM-3 和 PD-1/PD-L1 通路目前正在癌症免疫治疗中进行研究。这些免疫检查点在急性髓系白血病(AML)的白血病微环境中的相互作用仍不清楚。我们对 37 名新诊断的 AML 患者的骨髓进行了免疫表型研究。AML 白血病细胞上 TIM-3 表达水平高与首次 7+3 诱导失败(CR 16.2%,非 CR 36.4%,=0.038)相关。相比之下,NK 细胞上高水平的 TIM-3 与诱导后完全缓解(CR)状态相关(CR 24.7%,非 CR 6.5%,=0.035)。观察到的 PD-L1 阳性 AML 白血病细胞和 PD-1 或 PD-L1 阳性 NK 细胞很少。尽管在 28.3%的 T 细胞中检测到耗尽的 PD-1 表达 T 细胞,但很少检测到 PD-1 和 TIM-3 双重阳性的 T 细胞。总之,AML 白血病细胞和 NK 细胞上的 TIM-3 水平可能是 AML 的预后生物标志物。

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