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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1487792

CD56 neg CD16 + cells represent a distinct mature NK cell subset with altered phenotype and are associated with adverse clinical outcome upon expansion in AML

Provisionally accepted
Julia Wlosik Julia Wlosik 1*Florence ORLANDUCCI Florence ORLANDUCCI 1Manon Richaud Manon Richaud 1Clemence Demerle Clemence Demerle 2Amira Ben Amara Amira Ben Amara 1Marie-Sarah ROUVIERE Marie-Sarah ROUVIERE 1Philippe Livrati Philippe Livrati 1Laurent Gorvel Laurent Gorvel 1Marie-Anne Hospital Marie-Anne Hospital 2Nicolas Dulphy Nicolas Dulphy 3Raynier Devillier Raynier Devillier 2Norbert Vey Norbert Vey 2Daniel Olive Daniel Olive 1Anne-Sophie Chretien Anne-Sophie Chretien 1*
  • 1 INSERM U1068 Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France
  • 2 Institut Paoli-Calmettes (IPC), Marseille, Provence-Alpes-Côte d'Azur, France
  • 3 Institut de Recherche Saint Louis, Université de Paris, Paris, France

The final, formatted version of the article will be published soon.

    CD56 neg CD16 + Natural Killer (NK) cells have been reported to expand in chronic diseases and acute myeloid leukemia (AML). However, their biological role is still unclear. Using mass cytometry, spectral flow cytometry, bulk RNA-seq and in vitro assays, we characterized CD56 neg CD16 + NK cells that expand in AML. We confirmed that CD56 neg CD16 + NK cells represent a unique NK cell subset coexpressing Eomes and T-bet. CD56 neg CD16 + NK cells could recover CD56 expression in vitro where they displayed unaltered NK cell functions. We previously demonstrated that CD56 neg CD16 + NK cells expansion at diagnosis was associated with adverse clinical outcome in AML. Here, we validated our findings in a validation cohort of N=38 AML patients. AML patients with CD56 neg CD16 + NK cells expansion at diagnosis had decreased overall survival (HR[CI95]=5.5[1.2-24.5], p=0.0251) and relapse-free survival (HR[CI95]=13.1[1.9-87.5], p=0.0079) compared to AML patients without expansion after 36 months follow-up. RNA-seq unveiled that CD56 neg CD16 + NK cells were mature circulating NK cells with functional capacities. Upon expansion, CD56 neg CD16 + NK cells from AML patients showed altered proteomic phenotype, with increased frequency of terminally mature CD56 neg CD16 + NK cells expressing TIGIT along with decreased frequency of Siglec-7 + CD56 neg CD16 + NK cells. Taken together, our results suggest that CD56 neg CD16 + NK cells are a relevant target for future NK-cell-based immunotherapies.

    Keywords: CD56 neg NK cells, AML, high-dimensional cytometry, RNA-sequencing, Cancer

    Received: 28 Aug 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Wlosik, ORLANDUCCI, Richaud, Demerle, Ben Amara, ROUVIERE, Livrati, Gorvel, Hospital, Dulphy, Devillier, Vey, Olive and Chretien. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Julia Wlosik, INSERM U1068 Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France
    Anne-Sophie Chretien, INSERM U1068 Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France

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