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

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

doi:10.3389/fonc.2021.751834

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

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

Authors

Yang Xiao¹, Jinghong Chen², Jia Wang¹, Wei Guan¹, Mengzhen Wang¹, Linlin Zhang¹, Zhiding Wang³, Lixin Wang², Li Yu^{1

2}

Affiliations

¹ Department of Hematology and BMT Center, Chinese PLA General Hospital, Beijing, China.
² Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
³ Beijing Institute of Basic Medical Sciences, Beijing, China.

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 in vivo. This study suggests that a combination of the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.

Keywords: AML; ICAM-1; NK; immune escape; methylation.