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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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