Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer

Pinzon-Charry, A., Ho, C. S. K., Maxwell, T., McGuckin, M. A., Schmidt, C., Furnival, C., Pyke, C. M. and Lopez, J. A. (2007) Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer. British Journal of Cancer, 97 9: 1251-1259. doi:10.1038/sj.bjc.6604018


Author Pinzon-Charry, A.
Ho, C. S. K.
Maxwell, T.
McGuckin, M. A.
Schmidt, C.
Furnival, C.
Pyke, C. M.
Lopez, J. A.
Title Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 0007-0920
1532-1827
Publication date 2007
Sub-type Article (original research)
DOI 10.1038/sj.bjc.6604018
Open Access Status DOI
Volume 97
Issue 9
Start page 1251
End page 1259
Total pages 9
Editor A. Harris
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2008
Language eng
Abstract The generation of antitumour immunity depends on the nature of dendritic cell (DC)-tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n=137) and advanced (stage IV, n=36) disease compared to healthy controls (n=66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy.
Keyword Activation
Antigen
Breast cancer
Cd40 Ligand
Colony-stimulating Factor
Dendritic cells
Differentiation
Immune function
Immunotherapy CD40
Maturation
Nonsteroidal Antiestrogens Inhibit
Oncology
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Mon, 18 Feb 2008, 15:30:34 EST