NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML

Abstract

NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT).NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46high phenotype (p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression (p = 0.303).In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness.

Single-cell profiling reveals the trajectories of natural killer cell differentiation in bone marrow and a stress signature induced by acute myeloid leukemia

“…24,25 Conversely, higher levels of NKp30 and NKp46 on the cell surface have been linked to better outcomes. 26,27 Downregulation of other activating receptors, including DNAM-1, NKG2C and 2B4 [28][29][30] and upregulation of inhibitory receptors, such as NKG2A, 28,31 on the surface of NK cells from AML patients also contribute to the low cytotoxicity and IFN-γ secretion levels of these cells. 32 Here, we used unsupervised scRNAseq and unsupervised graphbased clustering to investigate human bone marrow NK cell heterogeneity under physiological conditions and at AML diagnosis.…”

Non-human Primate Determinants of Natural Killer Cells in Tissues at Steady-State and During Simian Immunodeficiency Virus Infection

“…The natural cytotoxicity receptors (NCRs) NKp46 and NKp44 have been described on both NK cells and ILCs (27). NKp46 is a major determinant of NK cell function and is implicated in tumor immune surveillance in acute myeloid leukemia (28,29). NKp44 is expressed on activated human NK cells and is important for tumor target cell recognition by NK cells during natural cytotoxicity responses, whereas, in the adult intestine, NKp44 + ILCs are the main ILC subset producing IL-22 (30,31).…”

Immune Escape after Hematopoietic Stem Cell Transplantation (HSCT): From Mechanisms to Novel Therapies

“…This has been demonstrated in AML patients with high NKp30 and NKp46 expression, which have a better overall survival (OS) and event-free survival (EFS) than those with low expression [64,65]. In patients submitted to allo-HSCT, a high expression of NKp46 has been associated with a significantly better prognosis [66,67].…”