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Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer
SIMPLE SUMMARY: CD8+ T lymphocytes are among the immune cells reputed to kill tumor cells. Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, w...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124419/ https://www.ncbi.nlm.nih.gov/pubmed/34066538 http://dx.doi.org/10.3390/cancers13092234 |
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author | Fenoglio, Daniela Belgioia, Liliana Parodi, Alessia Missale, Francesco Bacigalupo, Almalina Tarke, Alison Incandela, Fabiola Negrini, Simone Vecchio, Stefania Altosole, Tiziana Vlah, Sara Astone, Giuseppina Costabile, Francesca Ascoli, Alessandro Ferrera, Francesca Schenone, Guido De Palma, Raffaele Signori, Alessio Peretti, Giorgio Corvò, Renzo Filaci, Gilberto |
author_facet | Fenoglio, Daniela Belgioia, Liliana Parodi, Alessia Missale, Francesco Bacigalupo, Almalina Tarke, Alison Incandela, Fabiola Negrini, Simone Vecchio, Stefania Altosole, Tiziana Vlah, Sara Astone, Giuseppina Costabile, Francesca Ascoli, Alessandro Ferrera, Francesca Schenone, Guido De Palma, Raffaele Signori, Alessio Peretti, Giorgio Corvò, Renzo Filaci, Gilberto |
author_sort | Fenoglio, Daniela |
collection | PubMed |
description | SIMPLE SUMMARY: CD8+ T lymphocytes are among the immune cells reputed to kill tumor cells. Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of infiltrating CD8+ T cells in a cohort of 30 HNSCC patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28− T cells, and CD8+CD28−CD127−CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, we identified an intratumoral CD8+CD28- T cell subpopulation, which expressed markers of both exhausted (i.e., with impaired effector functions) and regulatory (i.e., exerting suppressive activities) cells. This suggests that in HNSCC effector T cells progressively undergo exhaustion and acquisition of regulatory properties, hampering their anti-tumor functions. ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28− T cells, and CD8+CD28−CD127−CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28− T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28−CD127−CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition. |
format | Online Article Text |
id | pubmed-8124419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81244192021-05-17 Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer Fenoglio, Daniela Belgioia, Liliana Parodi, Alessia Missale, Francesco Bacigalupo, Almalina Tarke, Alison Incandela, Fabiola Negrini, Simone Vecchio, Stefania Altosole, Tiziana Vlah, Sara Astone, Giuseppina Costabile, Francesca Ascoli, Alessandro Ferrera, Francesca Schenone, Guido De Palma, Raffaele Signori, Alessio Peretti, Giorgio Corvò, Renzo Filaci, Gilberto Cancers (Basel) Article SIMPLE SUMMARY: CD8+ T lymphocytes are among the immune cells reputed to kill tumor cells. Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of infiltrating CD8+ T cells in a cohort of 30 HNSCC patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28− T cells, and CD8+CD28−CD127−CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, we identified an intratumoral CD8+CD28- T cell subpopulation, which expressed markers of both exhausted (i.e., with impaired effector functions) and regulatory (i.e., exerting suppressive activities) cells. This suggests that in HNSCC effector T cells progressively undergo exhaustion and acquisition of regulatory properties, hampering their anti-tumor functions. ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28− T cells, and CD8+CD28−CD127−CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28− T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28−CD127−CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition. MDPI 2021-05-06 /pmc/articles/PMC8124419/ /pubmed/34066538 http://dx.doi.org/10.3390/cancers13092234 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fenoglio, Daniela Belgioia, Liliana Parodi, Alessia Missale, Francesco Bacigalupo, Almalina Tarke, Alison Incandela, Fabiola Negrini, Simone Vecchio, Stefania Altosole, Tiziana Vlah, Sara Astone, Giuseppina Costabile, Francesca Ascoli, Alessandro Ferrera, Francesca Schenone, Guido De Palma, Raffaele Signori, Alessio Peretti, Giorgio Corvò, Renzo Filaci, Gilberto Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer |
title | Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer |
title_full | Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer |
title_fullStr | Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer |
title_full_unstemmed | Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer |
title_short | Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer |
title_sort | development of exhaustion and acquisition of regulatory function by infiltrating cd8+cd28− t lymphocytes dictate clinical outcome in head and neck cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124419/ https://www.ncbi.nlm.nih.gov/pubmed/34066538 http://dx.doi.org/10.3390/cancers13092234 |
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