Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer
Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of...
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/PMC8458450/ https://www.ncbi.nlm.nih.gov/pubmed/34552178 http://dx.doi.org/10.1038/s42003-021-02595-z |
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author | Losurdo, Agnese Scirgolea, Caterina Alvisi, Giorgia Brummelman, Jolanda Errico, Valentina Di Tommaso, Luca Pilipow, Karolina Colombo, Federico Simone Fernandes, Bethania Peano, Clelia Testori, Alberto Tinterri, Corrado Roncalli, Massimo Santoro, Armando Mazza, Emilia Maria Cristina Lugli, Enrico |
author_facet | Losurdo, Agnese Scirgolea, Caterina Alvisi, Giorgia Brummelman, Jolanda Errico, Valentina Di Tommaso, Luca Pilipow, Karolina Colombo, Federico Simone Fernandes, Bethania Peano, Clelia Testori, Alberto Tinterri, Corrado Roncalli, Massimo Santoro, Armando Mazza, Emilia Maria Cristina Lugli, Enrico |
author_sort | Losurdo, Agnese |
collection | PubMed |
description | Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127− CD39(hi) Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39(lo) Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8(hi) ICOS(hi) IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs. |
format | Online Article Text |
id | pubmed-8458450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84584502021-10-07 Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer Losurdo, Agnese Scirgolea, Caterina Alvisi, Giorgia Brummelman, Jolanda Errico, Valentina Di Tommaso, Luca Pilipow, Karolina Colombo, Federico Simone Fernandes, Bethania Peano, Clelia Testori, Alberto Tinterri, Corrado Roncalli, Massimo Santoro, Armando Mazza, Emilia Maria Cristina Lugli, Enrico Commun Biol Article Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127− CD39(hi) Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39(lo) Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8(hi) ICOS(hi) IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs. Nature Publishing Group UK 2021-09-22 /pmc/articles/PMC8458450/ /pubmed/34552178 http://dx.doi.org/10.1038/s42003-021-02595-z Text en © The Author(s) 2021, corrected publication 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 Losurdo, Agnese Scirgolea, Caterina Alvisi, Giorgia Brummelman, Jolanda Errico, Valentina Di Tommaso, Luca Pilipow, Karolina Colombo, Federico Simone Fernandes, Bethania Peano, Clelia Testori, Alberto Tinterri, Corrado Roncalli, Massimo Santoro, Armando Mazza, Emilia Maria Cristina Lugli, Enrico Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer |
title | Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer |
title_full | Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer |
title_fullStr | Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer |
title_full_unstemmed | Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer |
title_short | Single-cell profiling defines the prognostic benefit of CD39(high) tissue resident memory CD8+ T cells in luminal-like breast cancer |
title_sort | single-cell profiling defines the prognostic benefit of cd39(high) tissue resident memory cd8+ t cells in luminal-like breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458450/ https://www.ncbi.nlm.nih.gov/pubmed/34552178 http://dx.doi.org/10.1038/s42003-021-02595-z |
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