Chretien Anne-Sophie, Devillier Raynier, Fauriat Cyril, Orlanducci Florence, Harbi Samia, Le Roy Aude, Rey Jérôme, Bouvier Borg Gaelle, Gautherot Emmanuel, Hamel Jean-François, Ifrah Norbert, Lacombe Catherine, Cornillet-Lefebvre Pascale, Delaunay Jacques, Toubert Antoine, Arnoulet Christine, Vey Norbert, Blaise Didier, Olive Daniel
Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068; CNRS, UMR7258, Institut Paoli-Calmettes; Aix-Marseille University, UM 105, Marseille, France.
Immunomonitoring platform, Institut Paoli-Calmettes, Marseille, France.
Oncoimmunology. 2017 Mar 24;6(12):e1307491. doi: 10.1080/2162402X.2017.1307491. eCollection 2017.
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 NKp46 phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46 phenotype (74.3% vs. 46.6%, = 0.014; 82.6% vs. 57.1%, = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, = 0.010) and PFS (HR = 0.335, = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46 phenotype ( = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression ( = 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.
NKp46是自然杀伤（NK）细胞功能的主要决定因素，并且与急性髓系白血病（AML）的肿瘤免疫监视有关。本研究的目的是调查NKp46表达在一个独立的AML患者队列中的预后意义，并研究NKp46对异基因干细胞移植（allo-SCT）后临床结局的影响。通过流式细胞术在诊断时评估NK细胞上的NKp46表达（N = 180例患者）。根据NKp46表达评估临床结局。诊断时具有NKp46表型的患者比具有NKp46表型的患者具有更好的无进展生存期（PFS）和总生存期（OS）（分别为74.3%对46.6%，P = 0.014；82.6%对57.1%，P = 0.010）。在多变量分析中，高NKp46是改善OS（HR = 0.409，P = 0.010）和PFS（HR = 0.335，P = 0.011）的独立因素。亚组分析显示，allo-SCT对具有NKp46表型的患者的PFS有有利影响（P = 0.025）。相比之下，allo-SCT对NKp46低表达患者的PFS没有影响（P = 0.303）。总之，我们验证了AML诊断时NKp46表达的预后价值。然而，NKp46表达的预后价值仅限于接受allo-SCT治疗的患者，因此表明NKp46状态可能预测allo-SCT反应性。
