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: https://orcid.org/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:	Number Type 10.1186/1479-5876-8-114 DOI 1479-5876-8-114 Publisher Item Identifier
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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