The Functional and Prognostic Impact of TIGIT Expression on Bone Marrow NK Cells in Core Binding Factor-Acute Myeloid Leukemia Patients at Diagnosis

TIGIT 表达对核心结合因子-急性髓系白血病患者诊断时骨髓 NK 细胞的功能和预后影响

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作者:Dai-Hong Xie, Jun Wang, Kai Sun, Zong-Yan Shi, Ya-Zhe Wang, Yan Chang, Xiao-Ying Yuan, Yan-Rong Liu, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Ya-Zhen Qin

Background

The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated.

Conclusions

TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients.

Methods

Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56bright, and CD56dim NK cell subsets after in vitro stimulation.

Results

The frequencies of TIGIT+ cells in total NK, CD56bright, and CD56dim NK cell subsets had no significant difference between patients and HDs. TNF-α and INF-γ levels were uniformly lower in TIGIT+ cells than the corresponding TIGIT- cells in all HDs, whereas those for TIGIT+ to TIGIT- cells in patients were highly heterogenous; TIGIT expression was not related to PFP and GZMB expression in HDs, whereas it was related to higher intracellular PFP and GZMB levels in patients. Patients' TIGIT+ NK cells displayed lower K562 cell-killing activity than their TIGIT- NK cells. In addition, high frequencies of TIGIT+ cells in total NK and CD56dim NK cells were associated with poor RFS. Conclusions: TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients.

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