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High-dimensional mass cytometry analysis of NK cell alterations in Acute Myeloid Leukemia identifies a subgroup with adverse clinical outcome

High-dimensional mass cytometry analysis of NK cell alterations in Acute Myeloid Leukemia identifies a subgroup with adverse clinical outcome

Authors :
Raynier Devillier
Daniel Olive
Cyril Fauriat
Norbert Vey
Julia Wlosik
Clemence Demerle
Emilie Gregori
Philippe Rochigneux
Magali Paul
Antoine Toubert
Marie Malissen
Florence Orlanducci
Nassim Salem
Hervé Luche
Thomas Pagliardini
Mathieu Morey
Nicolas Dulphy
Jacques A. Nunès
Didier Blaise
Samuel Granjeaud
Anne-Sophie Chretien
Charlotte Cordier
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

Natural killer (NK) cells are major anti-leukemic immune effectors. Leukemic blasts have a negative impact on NK cell function and promote the emergence of phenotypically and functionally impaired NK cells. In the present work, we highlight an accumulation of CD56-CD16+ unconventional NK cells in acute myeloid leukemia (AML), an aberrant subset initially described as being elevated in patients chronically infected with HIV-1. Deep phenotyping of NK cells was performed using peripheral blood from patients with newly-diagnosed AML (N=48, HEMATOBIO cohort, NCT02320656) and healthy subjects (N=18) by mass cytometry. We evidenced a moderate to drastic accumulation of CD56- CD16+ unconventional NK cells in 27% of patients. These NK cells displayed decreased expression of NKG2A as well as the triggering receptors NKp30, and NKp46, in line with previous observations in HIV-infected patients. High-dimensional characterization of these NK cells highlighted a decreased expression of three additional major triggering receptors required for NK cell activation, NKG2D, DNAM-1, and CD96. A high proportion of CD56-CD16+ NK cells at diagnosis was associated with an adverse clinical outcome, with decreased overall survival (HR=0.13; P=.0002) and event-free survival (HR=0.33; P=.018), and retained statistical significance in multivariate analysis. Pseudo-time analysis of the NK cell compartment highlighted a disruption of the maturation process, with a bifurcation from conventional NK cells toward CD56-CD16+ NK cells. Overall, our data suggest that the accumulation of CD56-CD16+ NK cells may be the consequence of immune escape from innate immunity during AML progression.SignificanceThis work provides the first report of accumulation of unconventional CD56-CD16+ NK cells in non-virally induced malignancies. Pseudotime analysis highlights a bifurcation point occurring during the course of NK cell maturation, providing elements regarding the possible origin of CD56-CD16+ NK cells. Increased frequency of CD56-CD16+ NK cells is associated with adverse clinical outcome in AML and might contribute, as well as other maturation defects, to a defective control of AML progression. Overall, accumulation of CD56-CD16+ NK cells could be an important feature of immune escape from innate immunity.Graphical abstractKey pointsA disruption in the maturation process of NK cells leads to accumulation of unconventional CD56- CD16+ NK cells in patients with AMLHigh frequency of CD56-CD16+ NK cells is associated with adverse clinical outcome

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........319c75f97969ae4713a289e1762d5af1
Full Text :
https://doi.org/10.1101/2020.10.01.20204867