Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and FcγRIIIa-Triggered Responses.

Autor: Wagner JA; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri., Berrien-Elliott MM; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri., Rosario M; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri., Leong JW; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri., Jewell BA; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri., Schappe T; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri., Abdel-Latif S; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri., Fehniger TA; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: tfehnige@wustl.edu.
Jazyk: angličtina
Zdroj: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2017 Mar; Vol. 23 (3), pp. 398-404. Date of Electronic Publication: 2016 Nov 25.
DOI: 10.1016/j.bbmt.2016.11.018
Abstrakt: Cytokine-induced memory-like natural killer (NK) cells differentiate after short-term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks after the initial preactivation. Conventional NK cell function depends on a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown. We investigated this interaction using killer cell immunoglobulin-like receptor- and HLA-genotyped primary human NK cells. Memory-like differentiation resulted in enhanced IFN-γ production triggered by leukemia targets or FcγRIIIa ligation within licensed NK cells, which exhibited the highest functionality of the NK cell subsets interrogated. IFN-γ production by unlicensed memory-like NK cells was also enhanced to a level comparable with that of licensed control NK cells. Mechanistically, differences in responses to FcγRIIIa-based triggering were not explained by alterations in key signaling intermediates, indicating that the underlying biology of memory-like NK cells is distinct from that of adaptive NK cells in human cytomegalovirus-positive individuals. Additionally, memory-like NK cells responded robustly to cytokine receptor restimulation with no impact of licensing status. These results demonstrate that both licensed and unlicensed memory-like NK cell populations have enhanced functionality, which may be translated to improve leukemia immunotherapy.
(Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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