Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer
Article first published online: 1 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 7, pages 1512–1519, 1 October 2007
How to Cite
Vudattu, N. K., Magalhaes, I., Schmidt, M., Seyfert-Margolis, V. and Maeurer, M. J. (2007), Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer. Int. J. Cancer, 121: 1512–1519. doi: 10.1002/ijc.22854
- Issue published online: 24 JUL 2007
- Article first published online: 1 JUN 2007
- Manuscript Accepted: 20 APR 2007
- Manuscript Received: 9 JAN 2007
- signal transduction;
- tumor immunity
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.