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EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia
Genome-wide association studies identified a single-nucleotide polymorphism (SNP) affecting the transcription factor Eomesodermin (EOMES) associated with a significantly increased risk to develop chronic lymphocytic leukemia (CLL). Epigenetic analyses, RNA sequencing, and flow cytometry revealed tha...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550953/ https://www.ncbi.nlm.nih.gov/pubmed/33731848 http://dx.doi.org/10.1038/s41375-021-01198-1 |
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author | Llaó-Cid, Laura Roessner, Philipp M. Chapaprieta, Vicente Öztürk, Selcen Roider, Tobias Bordas, Marie Izcue, Ana Colomer, Dolors Dietrich, Sascha Stilgenbauer, Stephan Hanna, Bola Martín-Subero, José Ignacio Seiffert, Martina |
author_facet | Llaó-Cid, Laura Roessner, Philipp M. Chapaprieta, Vicente Öztürk, Selcen Roider, Tobias Bordas, Marie Izcue, Ana Colomer, Dolors Dietrich, Sascha Stilgenbauer, Stephan Hanna, Bola Martín-Subero, José Ignacio Seiffert, Martina |
author_sort | Llaó-Cid, Laura |
collection | PubMed |
description | Genome-wide association studies identified a single-nucleotide polymorphism (SNP) affecting the transcription factor Eomesodermin (EOMES) associated with a significantly increased risk to develop chronic lymphocytic leukemia (CLL). Epigenetic analyses, RNA sequencing, and flow cytometry revealed that EOMES is not expressed in CLL cells, but in CD8(+) T cells for which EOMES is a known master regulator. We thus hypothesized that the increased CLL risk associated with the EOMES SNP might be explained by its negative impact on CD8(+) T-cell-mediated immune control of CLL. Flow cytometry analyses revealed a higher EOMES expression in CD8(+) T cells of CLL patients compared to healthy individuals, and an accumulation of PD-1(+) EOMES(+) CD8(+) T cells in lymph nodes rather than blood or bone marrow in CLL. This was in line with an observed expansion of EOMES(+) CD8(+) T cells in the spleen of leukemic Eµ-TCL1 mice. As EOMES expression was highest in CD8(+) T cells that express inhibitory receptors, an involvement of EOMES in T-cell exhaustion and dysfunction seems likely. Interestingly, Eomes-deficiency in CD8(+) T cells resulted in their impaired expansion associated with decreased CLL control in mice. Overall, these observations suggest that EOMES is essential for CD8(+) T-cell expansion and/or maintenance, and therefore involved in adaptive immune control of CLL. |
format | Online Article Text |
id | pubmed-8550953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85509532021-11-10 EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia Llaó-Cid, Laura Roessner, Philipp M. Chapaprieta, Vicente Öztürk, Selcen Roider, Tobias Bordas, Marie Izcue, Ana Colomer, Dolors Dietrich, Sascha Stilgenbauer, Stephan Hanna, Bola Martín-Subero, José Ignacio Seiffert, Martina Leukemia Article Genome-wide association studies identified a single-nucleotide polymorphism (SNP) affecting the transcription factor Eomesodermin (EOMES) associated with a significantly increased risk to develop chronic lymphocytic leukemia (CLL). Epigenetic analyses, RNA sequencing, and flow cytometry revealed that EOMES is not expressed in CLL cells, but in CD8(+) T cells for which EOMES is a known master regulator. We thus hypothesized that the increased CLL risk associated with the EOMES SNP might be explained by its negative impact on CD8(+) T-cell-mediated immune control of CLL. Flow cytometry analyses revealed a higher EOMES expression in CD8(+) T cells of CLL patients compared to healthy individuals, and an accumulation of PD-1(+) EOMES(+) CD8(+) T cells in lymph nodes rather than blood or bone marrow in CLL. This was in line with an observed expansion of EOMES(+) CD8(+) T cells in the spleen of leukemic Eµ-TCL1 mice. As EOMES expression was highest in CD8(+) T cells that express inhibitory receptors, an involvement of EOMES in T-cell exhaustion and dysfunction seems likely. Interestingly, Eomes-deficiency in CD8(+) T cells resulted in their impaired expansion associated with decreased CLL control in mice. Overall, these observations suggest that EOMES is essential for CD8(+) T-cell expansion and/or maintenance, and therefore involved in adaptive immune control of CLL. Nature Publishing Group UK 2021-03-17 2021 /pmc/articles/PMC8550953/ /pubmed/33731848 http://dx.doi.org/10.1038/s41375-021-01198-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Llaó-Cid, Laura Roessner, Philipp M. Chapaprieta, Vicente Öztürk, Selcen Roider, Tobias Bordas, Marie Izcue, Ana Colomer, Dolors Dietrich, Sascha Stilgenbauer, Stephan Hanna, Bola Martín-Subero, José Ignacio Seiffert, Martina EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia |
title | EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia |
title_full | EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia |
title_fullStr | EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia |
title_full_unstemmed | EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia |
title_short | EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia |
title_sort | eomes is essential for antitumor activity of cd8(+) t cells in chronic lymphocytic leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550953/ https://www.ncbi.nlm.nih.gov/pubmed/33731848 http://dx.doi.org/10.1038/s41375-021-01198-1 |
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