Could the Immune Modulation of Invariant Natural Killer T Cell and the Expression of CD244 and CD196 on Natural Killer Cell Subtypes Impact the Treatment Outcomes of Acute Myeloid Leukemia Patients?

Abstract

Background: The present study aimed to assess the CCR6 and CD244 expression on natural killer (NK) and natural killer T (NKT) cells, considering their different subsets and examining their associations with molecular cytogenetics and clinical outcomes in newly diagnosed adult acute myeloid leukemia (AML) patients.

Methods: We recruited 26 new cases of newly diagnosed adult AML and 24 adult healthy participants as controls, after diagnosis of AML, bone marrow studies, cytogenetics, and molecular studies; samples of peripheral blood were collected from all participants for flow cytometry to determine the expressions of CD244 and CD196.

Results: Invariant NKT cells were significantly more abundant in controls than in patients. In patients, CD244 expression was associated with increased accumulation of NKT cells, whereas CD196⁺ NKT cells were more frequently found in controls. Regarding CD3⁻ NK cells, co-expression of CD244 and CD196 was significantly increased in patients compared with controls across all CD3⁻ NK subpopulations. CD244 expression was higher in controls, within CD16^brightCD56^bright NK, CD16^brightCD56^dim NK, and CD16^dimCD56^bright NK subsets. In contrast, in patients’ CD16⁺CD56⁻ NK cells, CD196 showed an inverse pattern: it was expressed more in patients with CD16^brightCD56^dim NK cells, compared with controls’ CD16⁺CD56⁻ and CD16⁻CD56⁺ NK cells. Dim CD56 expression on NK cells, regardless of CD16 level, was associated with treatment remission. In addition, the presence of CD244 and/or CD196 was linked to treatment failure, whereas the dual absence of CD244 and CD196 was associated with remission.

Conclusion: The expression pattern of CD244 (2B4 receptor) and CD196 on NK and NKT cells was generally associated with remission status and prognostic features of AML patients.