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

Anne-Sophie Chrétien, Raynier Devillier, Samuel Granjeaud, Charlotte Cordier, Clémence Demerle, Nassim Salem, Julia Wlosik, Florence Orlanducci, Laurent Gorvel, Stéphane Fattori, Jihane Pakradouni, Emilie Gregori, Magali Paul, Philippe Rochigneux, Thomas Pagliardini, Mathieu Morey, Cyril Fauriat, Nicolas Dulphy, Antoine Toubert, Hervé Luche, Marie Malissen, Didier Blaise, Jacques A. Nunès, Norbert Vey, Daniel Olive

2021Proceedings of the National Academy of Sciences60 citationsDOIOpen Access PDF

Abstract

Significance This work provides a report of accumulation of unconventional CD56 − CD16 + NK cells in nonvirally induced malignancies. Increased frequency of CD56 − CD16 + NK cells is associated with adverse clinical outcome in AML, as well as other maturation defects, and might contribute to a defective control of AML progression. Pseudotime analysis highlights a disruption in the maturation process of conventional NK cells in AML patients, leading to a bifurcation point absent in healthy subjects. This analysis, combined with the reduced frequency of conventional NK cells observed in AML patients, suggests that unconventional CD56 − CD16 + NK cells derive from an aberrant maturation of conventional NK cells. Overall, accumulation of CD56 − CD16 + NK cells could be an important feature of immune escape from innate immunity.

Topics & Concepts

NKG2DCD16Mass cytometryInterleukin 21Natural killer cellJanus kinase 3ImmunologyK562 cellsFlow cytometryImmune systemNK-92Interleukin 12Innate immune systemLymphokine-activated killer cellMyeloid leukemiaBiologyCancer researchLeukemiaT cellCytotoxic T cellCD8PhenotypeIn vitroCD3GeneBiochemistryImmune Cell Function and InteractionT-cell and B-cell ImmunologyReproductive System and Pregnancy
High-dimensional mass cytometry analysis of NK cell alterations in AML identifies a subgroup with adverse clinical outcome | Litcius