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HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy
Human endogenous retroviruses (HERVs) represent 8% of the human genome. The expression of HERVs and their immune impact have not been extensively studied in Acute Myeloid Leukemia (AML). In this study, we used a reference of 14 968 HERV functional units to provide a thorough analysis of HERV express...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540360/ https://www.ncbi.nlm.nih.gov/pubmed/35759575 http://dx.doi.org/10.1002/ajh.26647 |
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author | Alcazer, Vincent Bonaventura, Paola Tonon, Laurie Michel, Emilie Mutez, Virginie Fabres, Clémentine Chuvin, Nicolas Boulos, Rasha Estornes, Yann Maguer‐Satta, Véronique Geistlich, Kevin Viari, Alain Metzeler, Klaus H. Hiddemann, Wolfgang Batch, Aarif M. N. Herold, Tobias Caux, Christophe Depil, Stéphane |
author_facet | Alcazer, Vincent Bonaventura, Paola Tonon, Laurie Michel, Emilie Mutez, Virginie Fabres, Clémentine Chuvin, Nicolas Boulos, Rasha Estornes, Yann Maguer‐Satta, Véronique Geistlich, Kevin Viari, Alain Metzeler, Klaus H. Hiddemann, Wolfgang Batch, Aarif M. N. Herold, Tobias Caux, Christophe Depil, Stéphane |
author_sort | Alcazer, Vincent |
collection | PubMed |
description | Human endogenous retroviruses (HERVs) represent 8% of the human genome. The expression of HERVs and their immune impact have not been extensively studied in Acute Myeloid Leukemia (AML). In this study, we used a reference of 14 968 HERV functional units to provide a thorough analysis of HERV expression in normal and AML bone marrow cells. We show that the HERV retrotranscriptome accurately characterizes normal and leukemic cell subpopulations, including leukemia stem cells, in line with different epigenetic profiles. We then show that HERV expression delineates AML subtypes with different prognoses. We finally propose a method to select and prioritize CD8(+) T cell epitopes derived from AML‐specific HERVs and we show that lymphocytes infiltrating patient bone marrow at diagnosis contain naturally occurring CD8(+) T cells against these HERV epitopes. We also provide in vitro data supporting the functionality of HERV‐specific CD8(+) T‐cells against AML cells. These results show that HERVs represent an important source of genetic information that can help enhancing disease stratification or biomarker identification and an important reservoir of alternative tumor‐specific T cell epitopes relevant for cancer immunotherapy. |
format | Online Article Text |
id | pubmed-9540360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95403602022-10-14 HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy Alcazer, Vincent Bonaventura, Paola Tonon, Laurie Michel, Emilie Mutez, Virginie Fabres, Clémentine Chuvin, Nicolas Boulos, Rasha Estornes, Yann Maguer‐Satta, Véronique Geistlich, Kevin Viari, Alain Metzeler, Klaus H. Hiddemann, Wolfgang Batch, Aarif M. N. Herold, Tobias Caux, Christophe Depil, Stéphane Am J Hematol Research Articles Human endogenous retroviruses (HERVs) represent 8% of the human genome. The expression of HERVs and their immune impact have not been extensively studied in Acute Myeloid Leukemia (AML). In this study, we used a reference of 14 968 HERV functional units to provide a thorough analysis of HERV expression in normal and AML bone marrow cells. We show that the HERV retrotranscriptome accurately characterizes normal and leukemic cell subpopulations, including leukemia stem cells, in line with different epigenetic profiles. We then show that HERV expression delineates AML subtypes with different prognoses. We finally propose a method to select and prioritize CD8(+) T cell epitopes derived from AML‐specific HERVs and we show that lymphocytes infiltrating patient bone marrow at diagnosis contain naturally occurring CD8(+) T cells against these HERV epitopes. We also provide in vitro data supporting the functionality of HERV‐specific CD8(+) T‐cells against AML cells. These results show that HERVs represent an important source of genetic information that can help enhancing disease stratification or biomarker identification and an important reservoir of alternative tumor‐specific T cell epitopes relevant for cancer immunotherapy. John Wiley & Sons, Inc. 2022-07-12 2022-09 /pmc/articles/PMC9540360/ /pubmed/35759575 http://dx.doi.org/10.1002/ajh.26647 Text en © 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Alcazer, Vincent Bonaventura, Paola Tonon, Laurie Michel, Emilie Mutez, Virginie Fabres, Clémentine Chuvin, Nicolas Boulos, Rasha Estornes, Yann Maguer‐Satta, Véronique Geistlich, Kevin Viari, Alain Metzeler, Klaus H. Hiddemann, Wolfgang Batch, Aarif M. N. Herold, Tobias Caux, Christophe Depil, Stéphane HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy |
title |
HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy |
title_full |
HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy |
title_fullStr |
HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy |
title_full_unstemmed |
HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy |
title_short |
HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy |
title_sort | hervs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540360/ https://www.ncbi.nlm.nih.gov/pubmed/35759575 http://dx.doi.org/10.1002/ajh.26647 |
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