Double Positive CD4+CD8+ T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization
| Autor: | Denise Nardelli-Haefliger, Ilaria Lucca, Massimo Valerio, Patrice Jichlinski, Sonia-Christina Rodrigues-Dias, Laurent Derré, Rodolfo Burruni, Florence Dartiguenave, Thomas Tawadros, Valérie Cesson, Perrine Bohner, Mathieu F. Chevalier |
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| Přispěvatelé: | Lausanne University Hospital, Lausanne university hospital |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
lcsh:Immunologic diseases. Allergy 0301 basic medicine 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 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 CD8 Antigens Immunology Double negative Context (language use) Biology Flow cytometry 03 medical and health sciences Prostate cancer Th2 Cells 0302 clinical medicine Immune system medicine Immunology and Allergy Cytotoxic T cell Original Research medicine.diagnostic_test Prostatic Neoplasms Cancer medicine.disease Kidney Neoplasms 3. Good health 030104 developmental biology Urinary Bladder Neoplasms CD4 Antigens Cancer research [SDV.IMM]Life Sciences [q-bio]/Immunology CD4 + CD8 + T cells lcsh:RC581-607 CD8 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Frontiers, 2019, 10, ⟨10.3389/fimmu.2019.00622⟩ Frontiers in Immunology, Vol 10 (2019) Frontiers in immunology, vol. 10, pp. 622 |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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