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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00622/full |
| _version_ | 1811208578960195584 |
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| author | Perrine Bohner Mathieu F. Chevalier Valérie Cesson Sonia-Christina Rodrigues-Dias Florence Dartiguenave Rodolfo Burruni Thomas Tawadros Massimo Valerio Ilaria Lucca Denise Nardelli-Haefliger Patrice Jichlinski Laurent Derré |
| author_facet | Perrine Bohner Mathieu F. Chevalier Valérie Cesson Sonia-Christina Rodrigues-Dias Florence Dartiguenave Rodolfo Burruni Thomas Tawadros Massimo Valerio Ilaria Lucca Denise Nardelli-Haefliger Patrice Jichlinski Laurent Derré |
| author_sort | Perrine Bohner |
| collection | DOAJ |
| 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 CD4highCD8low and CD4+CD8high DP T-cell subsets. Of note, most CD4highCD8low DP T cells show a CD8αα phenotype, whereas CD4+CD8high 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. |
| first_indexed | 2024-04-12T04:23:47Z |
| format | Article |
| id | doaj.art-c41749b545d04398905c137f403e3b53 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T04:23:47Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c41749b545d04398905c137f403e3b532022-12-22T03:48:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00622446867Double Positive CD4+CD8+ T Cells Are Enriched in Urological Cancers and Favor T Helper-2 PolarizationPerrine BohnerMathieu F. ChevalierValérie CessonSonia-Christina Rodrigues-DiasFlorence DartiguenaveRodolfo BurruniThomas TawadrosMassimo ValerioIlaria LuccaDenise Nardelli-HaefligerPatrice JichlinskiLaurent DerréThe 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 CD4highCD8low and CD4+CD8high DP T-cell subsets. Of note, most CD4highCD8low DP T cells show a CD8αα phenotype, whereas CD4+CD8high 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00622/fullCD4+CD8+ T cellsdouble positive T cellsTh2Th1bladder cancerprostate cancer |
| spellingShingle | Perrine Bohner Mathieu F. Chevalier Valérie Cesson Sonia-Christina Rodrigues-Dias Florence Dartiguenave Rodolfo Burruni Thomas Tawadros Massimo Valerio Ilaria Lucca Denise Nardelli-Haefliger Patrice Jichlinski Laurent Derré Double Positive CD4+CD8+ T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization Frontiers in Immunology CD4+CD8+ T cells double positive T cells Th2 Th1 bladder cancer prostate cancer |
| 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 | CD4+CD8+ T cells double positive T cells Th2 Th1 bladder cancer prostate cancer |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00622/full |
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