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Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization
The immune system plays a central role in cancer development, showing both anti-tumor and pro-tumor activities depending on the immune cell subsets and the disease context. While CD8 T cells are associated with a favorable outcome in most cancers, only T helper type 1 (Th1) CD4 T cells play a protec...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450069/ https://www.ncbi.nlm.nih.gov/pubmed/30984190 http://dx.doi.org/10.3389/fimmu.2019.00622 |
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author | Bohner, Perrine Chevalier, Mathieu F. Cesson, Valérie Rodrigues-Dias, Sonia-Christina Dartiguenave, Florence Burruni, Rodolfo Tawadros, Thomas Valerio, Massimo Lucca, Ilaria Nardelli-Haefliger, Denise Jichlinski, Patrice Derré, Laurent |
author_facet | Bohner, Perrine Chevalier, Mathieu F. Cesson, Valérie Rodrigues-Dias, Sonia-Christina Dartiguenave, Florence Burruni, Rodolfo Tawadros, Thomas Valerio, Massimo Lucca, Ilaria Nardelli-Haefliger, Denise Jichlinski, Patrice Derré, Laurent |
author_sort | Bohner, Perrine |
collection | PubMed |
description | The immune system plays a central role in cancer development, showing both anti-tumor and pro-tumor activities depending on the immune cell subsets and the disease context. While CD8 T cells are associated with a favorable outcome in most cancers, only T helper type 1 (Th1) CD4 T cells play a protective role, in contrast to Th2 CD4 T cells. Double positive (DP) CD4(+)CD8(+) T cells remain understudied, although they were already described in human cancers, with conflicting data regarding their role. Here, we quantified and phenotypically/functionally characterized DP T cells in blood from urological cancer patients. We analyzed blood leukocytes of 24 healthy donors (HD) and 114 patients with urological cancers, including bladder (n = 54), prostate (n = 31), and kidney (n = 29) cancer patients using 10-color flow cytometry. As compared to HD, levels of circulating DP T cells were elevated in all urological cancer patients, which could be attributed to increased frequencies of both CD4(high)CD8(low) and CD4(+)CD8(high) DP T-cell subsets. Of note, most CD4(high)CD8(low) DP T cells show a CD8αα phenotype, whereas CD4(+)CD8(high) cells express both CD8α and CD8β subunits. Functional properties were investigated using ex-vivo generated DP T-cell clones. DP T cells from patients were skewed toward an effector memory phenotype, along with enhanced Th2 cytokine production. Interestingly, both CD8αα and CD8αβ DP T cells were able to trigger Th2 polarization of naïve CD4 T cells, while restraining Th1 induction. Thus, these data highlight a previously unrecognized immunoregulatory mechanism involving DP CD4(+)CD8(+) T cells in urological cancers. |
format | Online Article Text |
id | pubmed-6450069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64500692019-04-12 Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization Bohner, Perrine Chevalier, Mathieu F. Cesson, Valérie Rodrigues-Dias, Sonia-Christina Dartiguenave, Florence Burruni, Rodolfo Tawadros, Thomas Valerio, Massimo Lucca, Ilaria Nardelli-Haefliger, Denise Jichlinski, Patrice Derré, Laurent Front Immunol Immunology The immune system plays a central role in cancer development, showing both anti-tumor and pro-tumor activities depending on the immune cell subsets and the disease context. While CD8 T cells are associated with a favorable outcome in most cancers, only T helper type 1 (Th1) CD4 T cells play a protective role, in contrast to Th2 CD4 T cells. Double positive (DP) CD4(+)CD8(+) T cells remain understudied, although they were already described in human cancers, with conflicting data regarding their role. Here, we quantified and phenotypically/functionally characterized DP T cells in blood from urological cancer patients. We analyzed blood leukocytes of 24 healthy donors (HD) and 114 patients with urological cancers, including bladder (n = 54), prostate (n = 31), and kidney (n = 29) cancer patients using 10-color flow cytometry. As compared to HD, levels of circulating DP T cells were elevated in all urological cancer patients, which could be attributed to increased frequencies of both CD4(high)CD8(low) and CD4(+)CD8(high) DP T-cell subsets. Of note, most CD4(high)CD8(low) DP T cells show a CD8αα phenotype, whereas CD4(+)CD8(high) cells express both CD8α and CD8β subunits. Functional properties were investigated using ex-vivo generated DP T-cell clones. DP T cells from patients were skewed toward an effector memory phenotype, along with enhanced Th2 cytokine production. Interestingly, both CD8αα and CD8αβ DP T cells were able to trigger Th2 polarization of naïve CD4 T cells, while restraining Th1 induction. Thus, these data highlight a previously unrecognized immunoregulatory mechanism involving DP CD4(+)CD8(+) T cells in urological cancers. Frontiers Media S.A. 2019-03-29 /pmc/articles/PMC6450069/ /pubmed/30984190 http://dx.doi.org/10.3389/fimmu.2019.00622 Text en Copyright © 2019 Bohner, Chevalier, Cesson, Rodrigues-Dias, Dartiguenave, Burruni, Tawadros, Valerio, Lucca, Nardelli-Haefliger, Jichlinski and Derré. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Bohner, Perrine Chevalier, Mathieu F. Cesson, Valérie Rodrigues-Dias, Sonia-Christina Dartiguenave, Florence Burruni, Rodolfo Tawadros, Thomas Valerio, Massimo Lucca, Ilaria Nardelli-Haefliger, Denise Jichlinski, Patrice Derré, Laurent Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization |
title | Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization |
title_full | Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization |
title_fullStr | Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization |
title_full_unstemmed | Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization |
title_short | Double Positive CD4(+)CD8(+) T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization |
title_sort | double positive cd4(+)cd8(+) t cells are enriched in urological cancers and favor t helper-2 polarization |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450069/ https://www.ncbi.nlm.nih.gov/pubmed/30984190 http://dx.doi.org/10.3389/fimmu.2019.00622 |
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