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Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Natural killer (NK) cells are key innate immunity effectors that play a major role in malignant cell destruction. Based on expression patterns of CD16, CD56, CD57, and CD94, three distinct NK cell maturation stages have been described, which differ in terms of cytokine secretion, tissue migration, a...

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Autores principales: Cianga, Vlad Andrei, Campos Catafal, Lydia, Cianga, Petru, Pavel Tanasa, Mariana, Cherry, Mohamad, Collet, Phillipe, Tavernier, Emmanuelle, Guyotat, Denis, Rusu, Cristina, Aanei, Carmen Mariana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112610/
https://www.ncbi.nlm.nih.gov/pubmed/33986753
http://dx.doi.org/10.3389/fimmu.2021.665541
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author Cianga, Vlad Andrei
Campos Catafal, Lydia
Cianga, Petru
Pavel Tanasa, Mariana
Cherry, Mohamad
Collet, Phillipe
Tavernier, Emmanuelle
Guyotat, Denis
Rusu, Cristina
Aanei, Carmen Mariana
author_facet Cianga, Vlad Andrei
Campos Catafal, Lydia
Cianga, Petru
Pavel Tanasa, Mariana
Cherry, Mohamad
Collet, Phillipe
Tavernier, Emmanuelle
Guyotat, Denis
Rusu, Cristina
Aanei, Carmen Mariana
author_sort Cianga, Vlad Andrei
collection PubMed
description Natural killer (NK) cells are key innate immunity effectors that play a major role in malignant cell destruction. Based on expression patterns of CD16, CD56, CD57, and CD94, three distinct NK cell maturation stages have been described, which differ in terms of cytokine secretion, tissue migration, and the ability to kill target cells. Our study addressed NK cell maturation in bone marrow under three conditions: a normal developmental environment, during pre-leukemic state (myelodysplastic syndrome, MDS), and during leukemic transformation (acute myeloblastic leukemia, AML). In this study, we used a new tool to perform multicolor flow cytometry data analysis, based on principal component analysis, which allowed the unsupervised, accurate discrimination of immature, mature, and hypermature NK subpopulations. An impaired NK/T cell distribution was observed in the MDS bone marrow microenvironment compared with the normal and AML settings, and a phenotypic shift from the mature to the immature state was observed in NK cells under both the MDS and AML conditions. Furthermore, an impaired NK cell antitumor response, resulting in changes in NK cell receptor expression (CD159a, CD158a, CD158b, and CD158e1), was observed under MDS and AML conditions compared with the normal condition. The results of this study provide evidence for the failure of this arm of the immune response during the pathogenesis of myeloid malignancies. NK cell subpopulations display a heterogeneous and discordant dynamic on the spectrum between normal and pathological conditions. MDS does not appear to be a simple, intermediate stage but rather serves as a decisive step for the mounting of an efficient or ineffective immune response, leading to either the removal of the tumor cells or to malignancy.
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spelling pubmed-81126102021-05-12 Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia Cianga, Vlad Andrei Campos Catafal, Lydia Cianga, Petru Pavel Tanasa, Mariana Cherry, Mohamad Collet, Phillipe Tavernier, Emmanuelle Guyotat, Denis Rusu, Cristina Aanei, Carmen Mariana Front Immunol Immunology Natural killer (NK) cells are key innate immunity effectors that play a major role in malignant cell destruction. Based on expression patterns of CD16, CD56, CD57, and CD94, three distinct NK cell maturation stages have been described, which differ in terms of cytokine secretion, tissue migration, and the ability to kill target cells. Our study addressed NK cell maturation in bone marrow under three conditions: a normal developmental environment, during pre-leukemic state (myelodysplastic syndrome, MDS), and during leukemic transformation (acute myeloblastic leukemia, AML). In this study, we used a new tool to perform multicolor flow cytometry data analysis, based on principal component analysis, which allowed the unsupervised, accurate discrimination of immature, mature, and hypermature NK subpopulations. An impaired NK/T cell distribution was observed in the MDS bone marrow microenvironment compared with the normal and AML settings, and a phenotypic shift from the mature to the immature state was observed in NK cells under both the MDS and AML conditions. Furthermore, an impaired NK cell antitumor response, resulting in changes in NK cell receptor expression (CD159a, CD158a, CD158b, and CD158e1), was observed under MDS and AML conditions compared with the normal condition. The results of this study provide evidence for the failure of this arm of the immune response during the pathogenesis of myeloid malignancies. NK cell subpopulations display a heterogeneous and discordant dynamic on the spectrum between normal and pathological conditions. MDS does not appear to be a simple, intermediate stage but rather serves as a decisive step for the mounting of an efficient or ineffective immune response, leading to either the removal of the tumor cells or to malignancy. Frontiers Media S.A. 2021-04-27 /pmc/articles/PMC8112610/ /pubmed/33986753 http://dx.doi.org/10.3389/fimmu.2021.665541 Text en Copyright © 2021 Cianga, Campos Catafal, Cianga, Pavel Tanasa, Cherry, Collet, Tavernier, Guyotat, Rusu and Aanei https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Immunology
Cianga, Vlad Andrei
Campos Catafal, Lydia
Cianga, Petru
Pavel Tanasa, Mariana
Cherry, Mohamad
Collet, Phillipe
Tavernier, Emmanuelle
Guyotat, Denis
Rusu, Cristina
Aanei, Carmen Mariana
Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia
title Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia
title_full Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia
title_fullStr Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia
title_full_unstemmed Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia
title_short Natural Killer Cell Subpopulations and Inhibitory Receptor Dynamics in Myelodysplastic Syndromes and Acute Myeloid Leukemia
title_sort natural killer cell subpopulations and inhibitory receptor dynamics in myelodysplastic syndromes and acute myeloid leukemia
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112610/
https://www.ncbi.nlm.nih.gov/pubmed/33986753
http://dx.doi.org/10.3389/fimmu.2021.665541
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