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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.
Afiliação
  • Bohner P; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Chevalier MF; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Cesson V; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Rodrigues-Dias SC; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Dartiguenave F; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Burruni R; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Tawadros T; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Valerio M; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Lucca I; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Nardelli-Haefliger D; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Jichlinski P; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Derré L; Urology Research Unit, Urology Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
Front Immunol ; 10: 622, 2019.
Article em En | MEDLINE | ID: mdl-30984190
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 CD8ß 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 CD8αß 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias da Bexiga Urinária / Antígenos CD4 / Antígenos CD8 / Células Th2 / Neoplasias Renais Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias da Bexiga Urinária / Antígenos CD4 / Antígenos CD8 / Células Th2 / Neoplasias Renais Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça