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Title

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

Authors
Salomé, Bérengère
Loyon, Romain
Suffiotti, Madeleine
Salvestrini, Valentina
Wyss, Tania
Vanoni, Giulia
Ruan, Dan Fu
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Published in Blood Advances. 2019, vol. 3, no. 22, p. 3674-3687
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.
Identifiers
PMID: 31765481
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Structures
Research groups Ciblage des lymphocytes sécrétant des cytokines (1015)
Groupe Seebach Jorg Dieter (transplantation et immunologie) (856)
Project FNS: Ambizione PZOOP3_161459
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(ISO format)
SALOMÉ, Bérengère et al. CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML. In: Blood Advances, 2019, vol. 3, n° 22, p. 3674-3687. doi: 10.1182/bloodadvances.2018030478 https://archive-ouverte.unige.ch/unige:132570

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Deposited on : 2020-03-19

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