CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML.

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State: Public
Version: Final published version
License: All rights reserved
Serval ID
serval:BIB_4BC26C680B22
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML.
Journal
Blood advances
Author(s)
Salomé B., Gomez-Cadena A., Loyon R., Suffiotti M., Salvestrini V., Wyss T., Vanoni G., Ruan D.F., Rossi M., Tozzo A., Tentorio P., Bruni E., Riether C., Jacobsen E.M., Jandus P., Conrad C., Hoenig M., Schulz A., Michaud K., Della Porta M.G., Salvatore S., Ho P.C., Gfeller D., Ochsenbein A., Mavilio D., Curti A., Marcenaro E., Steinle A., Horowitz A., Romero P., Trabanelli S., Jandus C.
ISSN
2473-9537 (Electronic)
ISSN-L
2473-9529
Publication state
Published
Issued date
26/11/2019
Peer-reviewed
Oui
Volume
3
Number
22
Pages
3674-3687
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
An understanding of natural killer (NK) cell physiology in acute myeloid leukemia (AML) has led to the use of NK cell transfer in patients, demonstrating promising clinical results. However, AML is still characterized by a high relapse rate and poor overall survival. In addition to conventional NKs that can be considered the innate counterparts of CD8 T cells, another family of innate lymphocytes has been recently described with phenotypes and functions mirroring those of helper CD4 T cells. Here, in blood and tissues, we identified a CD56+ innate cell population harboring mixed transcriptional and phenotypic attributes of conventional helper innate lymphoid cells (ILCs) and lytic NK cells. These CD56+ ILC1-like cells possess strong cytotoxic capacities that are impaired in AML patients at diagnosis but are restored upon remission. Their cytotoxicity is KIR independent and relies on the expression of TRAIL, NKp30, NKp80, and NKG2A. However, the presence of leukemic blasts, HLA-E-positive cells, and/or transforming growth factor-β1 (TGF-β1) strongly affect their cytotoxic potential, at least partially by reducing the expression of cytotoxic-related molecules. Notably, CD56+ ILC1-like cells are also present in the NK cell preparations used in NK transfer-based clinical trials. Overall, we identified an NK cell-related CD56+ ILC population involved in tumor immunosurveillance in humans, and we propose that restoring their functions with anti-NKG2A antibodies and/or small molecules inhibiting TGF-β1 might represent a novel strategy for improving current immunotherapies.
Pubmed
Web of science
Open Access
Yes
Create date
28/11/2019 12:06
Last modification date
15/09/2020 5:26
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