%0 Journal Article
%T In vivo Expansion of Na£żve CD4+CD25high FOXP3+ Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 Administration
%A Marc Beyer
%A Beatrix Schumak
%A Martin R. Weihrauch
%A Bettina Andres
%A Thomas Giese
%A Elmar Endl
%A Percy A. Knolle
%A Sabine Classen
%A Andreas Limmer
%A Joachim L. Schultze
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0030422
%X 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 na£żve 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 na£żve Treg-cell pool. Higher frequencies of T-cell receptor excision circles in na£żve Treg cells indicate IL-2 dependent thymic generation of na£żve 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 na£żve 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 na£żve Treg cells.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030422