Double Positive CD4<sup>+</sup>CD8<sup>+</sup> T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_4BC4F69D1158
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Double Positive CD4<sup>+</sup>CD8<sup>+</sup> T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization.
Journal
Frontiers in immunology
Author(s)
Bohner P., Chevalier M.F., Cesson V., Rodrigues-Dias S.C., Dartiguenave F., Burruni R., Tawadros T., Valerio M., Lucca I., Nardelli-Haefliger D., Jichlinski P., Derré L.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
10
Pages
622
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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 <sup>+</sup> CD8 <sup>+</sup> 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 <sup>high</sup> CD8 <sup>low</sup> and CD4 <sup>+</sup> CD8 <sup>high</sup> DP T-cell subsets. Of note, most CD4 <sup>high</sup> CD8 <sup>low</sup> DP T cells show a CD8αα phenotype, whereas CD4 <sup>+</sup> CD8 <sup>high</sup> 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 <sup>+</sup> CD8 <sup>+</sup> T cells in urological cancers.
Keywords
Aged, Aged, 80 and over, CD4 Antigens/blood, CD4 Antigens/immunology, CD8 Antigens/blood, CD8 Antigens/immunology, Female, Flow Cytometry, Humans, Kidney Neoplasms/blood, Kidney Neoplasms/immunology, Kidney Neoplasms/pathology, Male, Middle Aged, Prostatic Neoplasms/blood, Prostatic Neoplasms/immunology, Prostatic Neoplasms/pathology, Th2 Cells/immunology, Th2 Cells/metabolism, Th2 Cells/pathology, Urinary Bladder Neoplasms/blood, Urinary Bladder Neoplasms/immunology, Urinary Bladder Neoplasms/pathology, CD4+CD8+ T cells, Th1, Th2, bladder cancer, double positive T cells, kidney cancer, prostate cancer
Pubmed
Web of science
Open Access
Yes
Create date
28/04/2019 15:55
Last modification date
26/08/2020 6:22
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