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急性髓系白血病通过细胞间黏附分子-1实现对自然杀伤细胞的表观遗传免疫逃逸

Acute Myeloid Leukemia Epigenetic Immune Escape From Nature Killer Cells by ICAM-1.

作者信息

Xiao Yang, Chen Jinghong, Wang Jia, Guan Wei, Wang Mengzhen, Zhang Linlin, Wang Zhiding, Wang Lixin, Yu Li

机构信息

Department of Hematology and BMT Center, Chinese PLA General Hospital, Beijing, China.

Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.

出版信息

Front Oncol. 2021 Oct 13;11:751834. doi: 10.3389/fonc.2021.751834. eCollection 2021.

Abstract

Acute myeloid leukemia (AML), a malignant disorder of hemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions, and epigenetic modification, while the mechanism is not clearly understood. Here we show that the expression of Intercellular adhesion molecule-1 (ICAM-1, CD54) is silenced in AML cells. Decitabine could upregulate ICAM-1 expression, which contributes to the NK-AML cell conjugates and helps NK cells kill AML cells. We also show that ICAM-1 high expression can reverse the AML immune evasion and activate NK cells function . This study suggests that a combination of the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.

摘要

急性髓系白血病(AML)是一种造血干细胞的恶性疾病。AML可通过基因突变、融合和表观遗传修饰逃避自然杀伤(NK)细胞的免疫监视,但其机制尚不清楚。在此我们表明,细胞间黏附分子-1(ICAM-1,CD54)在AML细胞中表达沉默。地西他滨可上调ICAM-1表达,这有助于NK-AML细胞结合,并帮助NK细胞杀伤AML细胞。我们还表明,ICAM-1高表达可逆转AML的免疫逃逸并激活NK细胞功能。本研究提示,去甲基化药物与NK细胞输注联合应用可能是治愈AML的一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b603/8548470/9a5fc3d4bae5/fonc-11-751834-g001.jpg

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