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- Title
In vivo Expansion of Naïve CD4<sup>+</sup>CD25<sup>high</sup> FOXP3<sup>+</sup> Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 Administration.
- Authors
Beyer, Marc; Schumak, Beatrix; Weihrauch, Martin R.; Andres, Bettina; Giese, Thomas; Endl, Elmar; Knolle, Percy A.; Classen, Sabine; Limmer, Andreas; Joachim L. Schultze
- Abstract
Regulatory T cells (Treg cells) are increased in context of malignancies and their expansion can be correlated with higher disease burden and decreased survival. Initially, interleukin 2 (IL-2) has been used as T-cell growth factor in clinical vaccination trials. In murine models, however, a role of IL-2 in development, differentiation, homeostasis, and function of Treg cells was established. In IL-2 treated cancer patients a further Treg-cell expansion was described, yet, the mechanism of expansion is still elusive. Here we report that functional Treg cells of a naïve phenotype - as determined by CCR7 and CD45RA expression - are significantly expanded in colorectal cancer patients. Treatment of 15 UICC stage IV colorectal cancer patients with IL-2 in a phase I/II peptide vaccination trial further enlarges the already increased naïve Treg-cell pool. Higher frequencies of T-cell receptor excision circles in naïve Treg cells indicate IL-2 dependent thymic generation of naïve Treg cells as a mechanism leading to increased frequencies of Treg cells post IL-2 treatment in cancer patients. This finding could be confirmed in naïve murine Treg cells after IL-2 administration. These results point to a more complex regulation of Treg cells in context of IL-2 administration. Future strategies therefore might aim at combining IL-2 therapy with novel strategies to circumvent expansion and differentiation of naïve Treg cells.
- Subjects
CANCER patients; CELLULAR mechanics; REGULATION of cell growth; CANCER treatment; GROWTH factors; CELL receptors; CYTOKINES
- Publication
PLoS ONE, 2012, Vol 7, Issue 1, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0030422