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

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. 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, CD56^bright, and CD56^dim NK cell subsets after in vitro stimulation. Results: The frequencies of TIGIT⁺ cells in total NK, CD56^bright, and CD56^dim 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 CD56^dim 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.