Bonanno, G., Procoli, A., Mariotti, A., Corallo, M., Perillo, A., Danese, S., De Cristofaro, R., Scambia, G. and Rutella, S. ORCID: 0000-0003-1970-7375, 2010. Effects of pegylated G-CSF on immune cell number and function in patients with gynecological malignancies. Journal of Translational Medicine, 8 (1), p. 114. ISSN 1479-5876
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Abstract
Background:
Pegylated granulocyte colony-stimulating factor (G-CSF; pegfilgrastim) is a longer-acting form of G-CSF, whose effects on dendritic cell (DC) and regulatory T cell (Treg) mobilization, and on the in vivo and ex vivo release of immune modulating cytokines remain unexplored.
Methods:
Twelve patients with gynecological cancers received carboplatin/paclitaxel chemotherapy and single-dose pegfilgrastim as prophylaxis of febrile neutropenia. Peripheral blood was collected prior to pegfilgrastim administration (day 0) and on days +7, +11 and +21, to quantify immunoregulatory cytokines and to assess type 1 DC (DC1), type 2 DC (DC2) and Treg cell mobilization. In vitro-differentiated, monocyte-derived DC were used to investigate endocytic activity, expression of DC maturation antigens and ability to activate allogeneic T-cell proliferation.
Results:
Pegfilgrastim increased the frequency of circulating DC1 and DC2 precursors. In contrast, CD4+FoxP3+bona fide Treg cells were unchanged compared with baseline. Serum levels of hepatocyte growth factor and interleukin (IL)-12p40, but not transforming growth factor-β1 or immune suppressive kynurenines, significantly increased after pegfilgrastim administration. Interestingly, pegfilgrastim fostered in vitro monocytic secretion of IL-12p40 and IL-12p70 when compared with unconjugated G-CSF. Finally, DC populations differentiated in vitro after clinical provision of pegfilgrastim were phenotypically mature, possessed low endocytic activity, and incited a robust T-cell proliferative response.
Conclusions:
Pegfilgrastim induced significant changes in immune cell number and function. The enhancement of monocytic IL-12 secretion portends favorable implications for pegfilgrastim administration to patients with cancer, a clinical context where the induction of immune deviation would be highly undesirable.
Item Type: | Journal article | ||||||
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Publication Title: | Journal of Translational Medicine | ||||||
Creators: | Bonanno, G., Procoli, A., Mariotti, A., Corallo, M., Perillo, A., Danese, S., De Cristofaro, R., Scambia, G. and Rutella, S. | ||||||
Publisher: | BioMed Central | ||||||
Date: | 9 November 2010 | ||||||
Volume: | 8 | ||||||
Number: | 1 | ||||||
ISSN: | 1479-5876 | ||||||
Identifiers: |
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Divisions: | Schools > School of Science and Technology | ||||||
Record created by: | Linda Sullivan | ||||||
Date Added: | 13 Sep 2016 13:23 | ||||||
Last Modified: | 09 Jun 2017 14:05 | ||||||
URI: | https://irep.ntu.ac.uk/id/eprint/28503 |
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