Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer

✍ Scribed by Nalini Kumar Vudattu; Isabelle Magalhaes; Marcus Schmidt; Vicki Seyfert-Margolis; Markus J. Maeurer

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 364 KB
• Volume: 121
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22854

✦ Synopsis

Abstract

Interleukin‐7‐receptor‐signaling plays a pivotal role in T‐cell development and maintenance of T‐cell memory. We studied IL‐7Rα (CD127) expression in PBMCs obtained from patients with breast cancer and examined IL‐7 receptor‐mediated downstream effects defined by STAT5 phosphorylation (p‐STAT5). Reduced numbers of IL‐7Rα‐positive cells were identified in CD4+ T‐cells as well as in a CD8+ T‐cell subset defined by CD8α/α homodimer expression in patients with breast cancer. PBMCs obtained from healthy donors (n = 19) and from patients with breast cancer (n = 19) exhibited constitutive p‐STAT5 expression in the range of 0–6.4% in CD4+ T‐cells and 0–4% in CD8+ T‐cells. Stimulation with recombinant human IL‐7 for 15 min increased p‐STAT5 expression up to 36–97% in CD4+T‐cells and to 26–90% in CD8+T‐cells obtained from healthy control donors (n = 19). In contrast, PBMCs obtained from 13/19 patients with breast cancer did not respond to IL‐7 as defined by STAT5 phosphorylation, despite expression of IL‐7Rα on T‐lymphocytes. T‐cells were further characterized for IL‐ 2 and IFN‐γ production induced by PMA/Ionomycin. PBMCs from 9/19 patients with breast cancer showed decreased IL‐2 and IFN‐γ production combined with IL‐7‐signaling defects; PBMCs from 4 patients with breast cancer exhibited deficient IL‐7‐signaling, yet intact cytokine production. Reduced numbers of IL‐7Rα‐positive cells and nonresponsiveness to IL‐7, defined by lack of STAT5 phosphorylation, characterizes the immunological profile in T‐cells from patients with breast cancer. © 2007 Wiley‐Liss, Inc.