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 NKp46^high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46^low 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 NKp46^high 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.

KEYWORDS:

• Allo-SCT
• AML
• NCR
• NK
• NKp46

Authors' disclosures of potential conflicts of interest

Anne-Sophie Chretien: Patents, Royalties, Other Intellectual Property : Inserm Transfert. Raynier Devilliers: No relationship to disclose. Cyril Fauriat: Patents, Royalties, Other Intellectual Property : Inserm Transfert. Florence Orlanducci: No relationship to disclose. Samia Harbi: No relationship to disclose. Aude Le Roy: No relationship to disclose. Jérôme Rey: Consulting or Advisory Role: Novartis. Travel, Accommodations, Expenses : Novartis. Gaelle Bouvier Borg: Employment: Immunotech Beckman Coulter. Emmanuel Gautherot: Employment: Immunotech Beckman Coulter. Jean-François Hamel: No relationship to disclose. Norbert Ifrah: No relationship to disclose. Catherine Lacombe: No relationship to disclose. Pascale Cornillet-Lefebvre: No relationship to disclose. Jacques Delaunay: No relationship to disclose. Antoine Toubert: No relationship to disclose. Christine Arnoulet: Patents, Royalties, Other Intellectual Property : Inserm Transfert. Norbert Vey: Consulting or Advisory Role : Novartis, Roche. Travel, Accommodations, Expenses : Amgen, Novartis Patents, Royalties, Other Intellectual Property : Inserm Transfert. Didier Blaise: Patents, Royalties, Other Intellectual Property : Inserm Transfert. Daniel Olive: Stock or Other Ownership : Imcheck Therapeutics. Research Funding : GSK. Patents, Royalties, Other Intellectual Property : Inserm Transfert, GSK.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors thank Beckman Coulter for their technical advices and for providing the antibodies used in this study. The authors thank the Paoli Calmettes Institute immunomonitoring platform for their valued contributions to this work. The authors thank the Groupe Ouest Est d'Etude des Leucémies Aiguës et autres Maladies du Sang (GOELAMS), the FILOtheque AML (N° BB-0033–00073), and Lamya Haddaoui, for their implication in this study.

Funding

This work has been financially supported by the INCa, the SIRIC (grant INCa-DGOS-INSERM 6038), the GS IBiSA. D.O. team was labeled “Equipe FRM DEQ 201 40329534.” D.O. is Senior Scholar of the Institut Universitaire de France. All antibodies used were kindly provided by Beckman-Coulter, Marseille, France. Beckman Coulter and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. All other trademarks are the property of their respective owners.