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

Abstract : Natural killer (NK) cells are major antileukemic 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 current 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 showed evidence of 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 and decreased overall survival (HR = 0.13; P = 0.0002) and event-free survival (HR = 0.33; P = 0.018) and retained statistical significance in multivariate analysis. Pseudotime 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.
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Submitted on : Friday, February 11, 2022 - 12:10:33 PM
Last modification on : Tuesday, June 7, 2022 - 5:16:01 PM

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Anne-Sophie Chretien, Raynier Devillier, Samuel Granjeaud, Charlotte Cordier, Clemence Demerle, et al.. High-dimensional mass cytometry analysis of NK cell alterations in AML identifies a subgroup with adverse clinical outcome. Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2021, 118 (22), pp.e2020459118. ⟨10.1073/pnas.2020459118⟩. ⟨hal-03565991⟩

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