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Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse

Recent studies have attempted to uncover the role of Group 1 Innate lymphoid cells (ILCs) in multiple physiological contexts, including cancer. However, the definition and precise contribution of Group 1 ILCs (constituting ILC1 and NK subsets) to metastasis is unclear due to the lack of well-defined...

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Autores principales: Verma, Riva, Er, Jun Zhi, Pu, Ren Wei, Sheik Mohamed, Jameelah, Soo, Ross A., Muthiah, Harish Mithiran, Tam, John Kit Chung, Ding, Jeak Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311635/
https://www.ncbi.nlm.nih.gov/pubmed/32625207
http://dx.doi.org/10.3389/fimmu.2020.01190
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author Verma, Riva
Er, Jun Zhi
Pu, Ren Wei
Sheik Mohamed, Jameelah
Soo, Ross A.
Muthiah, Harish Mithiran
Tam, John Kit Chung
Ding, Jeak Ling
author_facet Verma, Riva
Er, Jun Zhi
Pu, Ren Wei
Sheik Mohamed, Jameelah
Soo, Ross A.
Muthiah, Harish Mithiran
Tam, John Kit Chung
Ding, Jeak Ling
author_sort Verma, Riva
collection PubMed
description Recent studies have attempted to uncover the role of Group 1 Innate lymphoid cells (ILCs) in multiple physiological contexts, including cancer. However, the definition and precise contribution of Group 1 ILCs (constituting ILC1 and NK subsets) to metastasis is unclear due to the lack of well-defined cell markers. Here, we first identified ILC1 and NK cells in NSCLC patient blood and differentiated them based on the expression of transcription factors, T-bet and Eomes. Interestingly, Eomes downregulation in the peripheral blood NK cells of NSCLC patients positively correlated with disease progression. Additionally, we noted higher Eomes expression in NK cells (T-bet(+)Eomes(hi)) compared to ILC1s (T-bet(+)Eomes(lo)). We asked whether the decrease in Eomes was associated with the conversion of NK cells into ILC1 using Eomes as a reliable marker to differentiate ILC1s from NK cells. Utilizing a murine model of experimental metastasis, we observed an association between increase in metastasis and Eomes downregulation in NKp46(+)NK1.1(+) Group 1 ILCs, which was consistent to that of human NSCLC samples. Further confirmation of this trend was achieved by flow cytometry, which identified tissue-specific Eomes(lo) ILC1-like and Eomes(hi) NK-like subsets in the murine metastatic lung based on cell surface markers and adoptive transfer experiments. Next, functional characterization of these cell subsets showed reduced cytotoxicity and IFNγ production in Eomes(lo) ILC1s compared to Eomes(hi) cells, suggesting that lower Eomes levels are associated with poor cancer immunosurveillance by Group 1 ILCs. These findings provide novel insights into the regulation of Group 1 ILC subsets during metastasis, through the use of Eomes as a reliable marker to differentiate between NK and ILC1s.
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spelling pubmed-73116352020-07-02 Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse Verma, Riva Er, Jun Zhi Pu, Ren Wei Sheik Mohamed, Jameelah Soo, Ross A. Muthiah, Harish Mithiran Tam, John Kit Chung Ding, Jeak Ling Front Immunol Immunology Recent studies have attempted to uncover the role of Group 1 Innate lymphoid cells (ILCs) in multiple physiological contexts, including cancer. However, the definition and precise contribution of Group 1 ILCs (constituting ILC1 and NK subsets) to metastasis is unclear due to the lack of well-defined cell markers. Here, we first identified ILC1 and NK cells in NSCLC patient blood and differentiated them based on the expression of transcription factors, T-bet and Eomes. Interestingly, Eomes downregulation in the peripheral blood NK cells of NSCLC patients positively correlated with disease progression. Additionally, we noted higher Eomes expression in NK cells (T-bet(+)Eomes(hi)) compared to ILC1s (T-bet(+)Eomes(lo)). We asked whether the decrease in Eomes was associated with the conversion of NK cells into ILC1 using Eomes as a reliable marker to differentiate ILC1s from NK cells. Utilizing a murine model of experimental metastasis, we observed an association between increase in metastasis and Eomes downregulation in NKp46(+)NK1.1(+) Group 1 ILCs, which was consistent to that of human NSCLC samples. Further confirmation of this trend was achieved by flow cytometry, which identified tissue-specific Eomes(lo) ILC1-like and Eomes(hi) NK-like subsets in the murine metastatic lung based on cell surface markers and adoptive transfer experiments. Next, functional characterization of these cell subsets showed reduced cytotoxicity and IFNγ production in Eomes(lo) ILC1s compared to Eomes(hi) cells, suggesting that lower Eomes levels are associated with poor cancer immunosurveillance by Group 1 ILCs. These findings provide novel insights into the regulation of Group 1 ILC subsets during metastasis, through the use of Eomes as a reliable marker to differentiate between NK and ILC1s. Frontiers Media S.A. 2020-06-17 /pmc/articles/PMC7311635/ /pubmed/32625207 http://dx.doi.org/10.3389/fimmu.2020.01190 Text en Copyright © 2020 Verma, Er, Pu, Sheik Mohamed, Soo, Muthiah, Tam and Ding. http://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
Verma, Riva
Er, Jun Zhi
Pu, Ren Wei
Sheik Mohamed, Jameelah
Soo, Ross A.
Muthiah, Harish Mithiran
Tam, John Kit Chung
Ding, Jeak Ling
Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse
title Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse
title_full Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse
title_fullStr Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse
title_full_unstemmed Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse
title_short Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse
title_sort eomes expression defines group 1 innate lymphoid cells during metastasis in human and mouse
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311635/
https://www.ncbi.nlm.nih.gov/pubmed/32625207
http://dx.doi.org/10.3389/fimmu.2020.01190
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