In vivo Expansion of Naïve CD4 CD25high FOXP3 Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 AdministrationReportar como inadecuado




In vivo Expansion of Naïve CD4 CD25high FOXP3 Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 Administration - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Marc Beyer , Beatrix Schumak, Martin R. Weihrauch, Bettina Andres, Thomas Giese, Elmar Endl, Percy A. Knolle, Sabine Classen, And

Fuente: http://plos.srce.hr/



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