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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 22; pp. 1 - 11
• Main Authors: Chretien, Anne-Sophie, Devillier, Raynier, Granjeaud, Samuel, Cordier, Charlotte, Demerle, Clemence, Salem, Nassim, Wlosik, Julia, Orlanducci, Florence, Gorvel, Laurent, Fattori, Stephane, Hospital, Marie-Anne, Pakradouni, Jihane, Gregori, Emilie, Paul, Magali, Rochigneux, Philippe, Pagliardini, Thomas, Morey, Mathieu, Fauriat, Cyril, Dulphy, Nicolas, Toubert, Antoine, Luche, Herve, Malissen, Marie, Blaise, Didier, Nunès, Jacques A., Vey, Norbert, Olive, Daniel
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 01.06.2021
• Subjects: Accumulation; Acute myeloid leukemia; Anticancer properties; Biological Sciences; CD16 antigen; CD226 antigen; CD56 antigen; Cell activation; Clinical outcomes; Cytometry; Dimensional analysis; HIV; Human immunodeficiency virus; Innate immunity; Leukemia; Life Sciences; Medical Sciences; Multivariate analysis; Myeloid leukemia; Natural killer cells; NKG2 antigen; Peripheral blood; Phenotyping; Receptors; Subgroups; Survival; AML; natural killer cells; CD16; NK cells; mass cytometry; CD56; CD56−CD16+ NK cells
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2020459118

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 infectedwith 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 amoderate 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.