Effects of pegylated G-CSF on immune cell number and function in patients with gynecological malignancies

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
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:
NumberType
10.1186/1479-5876-8-114DOI
1479-5876-8-114Publisher Item Identifier
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 13 Sep 2016 13:23
Last Modified: 09 Jun 2017 14:05
URI: http://irep.ntu.ac.uk/id/eprint/28503

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