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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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01190/full |
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| author | Riva Verma Jun Zhi Er Ren Wei Pu Jameelah Sheik Mohamed Ross A. Soo Harish Mithiran Muthiah John Kit Chung Tam John Kit Chung Tam Jeak Ling Ding |
| author_facet | Riva Verma Jun Zhi Er Ren Wei Pu Jameelah Sheik Mohamed Ross A. Soo Harish Mithiran Muthiah John Kit Chung Tam John Kit Chung Tam Jeak Ling Ding |
| author_sort | Riva Verma |
| collection | DOAJ |
| 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+Eomeshi) compared to ILC1s (T-bet+Eomeslo). 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 Eomeslo ILC1-like and Eomeshi 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 Eomeslo ILC1s compared to Eomeshi 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. |
| first_indexed | 2024-12-13T12:01:48Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T12:01:48Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a7056f854d414aecaa01f274ff017b2c2022-12-21T23:47:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.01190537767Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and MouseRiva Verma0Jun Zhi Er1Ren Wei Pu2Jameelah Sheik Mohamed3Ross A. Soo4Harish Mithiran Muthiah5John Kit Chung Tam6John Kit Chung Tam7Jeak Ling Ding8Department of Biological Sciences, National University of Singapore, Singapore, SingaporeDepartment of Biological Sciences, National University of Singapore, Singapore, SingaporeDepartment of Biological Sciences, National University of Singapore, Singapore, SingaporeDivision of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Haematology-Oncology, National University Cancer Institute, Singapore, SingaporeDivision of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDivision of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Cardiac, Thoracic and Vascular Surgery, Singapore, SingaporeDepartment of Biological Sciences, National University of Singapore, Singapore, SingaporeRecent 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+Eomeshi) compared to ILC1s (T-bet+Eomeslo). 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 Eomeslo ILC1-like and Eomeshi 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 Eomeslo ILC1s compared to Eomeshi 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.01190/fullEomesoderminGroup 1 ILCsInnate Lymphoid Cellsmetastasisnon-small cell lung cancer |
| spellingShingle | Riva Verma Jun Zhi Er Ren Wei Pu Jameelah Sheik Mohamed Ross A. Soo Harish Mithiran Muthiah John Kit Chung Tam John Kit Chung Tam Jeak Ling Ding Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse Frontiers in Immunology Eomesodermin Group 1 ILCs Innate Lymphoid Cells metastasis non-small cell lung cancer |
| 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 | Eomesodermin Group 1 ILCs Innate Lymphoid Cells metastasis non-small cell lung cancer |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01190/full |
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