Tumours have at least two mechanisms that can alter dendritic cell (DC) maturation and function. The first affects the ability of haematopoietic progenitors to differentiate into functional DCs; the second affects their differentiation from CD14+ monocytes, promoting an early but dysfunctional maturation. The aim of this study was to evaluate the in vivo relevance of these pathways in breast cancer patients. For this purpose, 53 patients with invasive breast cancer were compared to 68 healthy controls. To avoid isolation or culture procedures for enrichment of DCs, analyses were directly performed by flow cytometry on whole-blood samples. The expression of surface antigens and intracellular accumulation of regulatory cytokines upon LPS stimulation were evaluated. The number of DCs, and in particular of the myeloid subpopulation, was markedly reduced in cancer patients (P < 0.001). Patient DCs were characterized by a more mature phenotype compared with controls (P = 0.016), and had impaired production of IL-12 (P < 0.001), These alterations were reverted by surgical resection of the tumour. To investigate the possible role of some tumour-related immunoactive soluble factors, we measured the plasmatic levels of vascular endothelial growth factor, IL-10 and spermine. A significant inverse correlation between spermine concentration and the percentage of DCs expressing IL-12 was found. Evidence was also obtained that in vitro exposure of monocyte-derived DCs to spermine promoted their activation and maturation, and impaired their function. Taken together, our results suggest that both the above-described mechanisms could concomitantly act in breast cancer to affect DC differentiation, and that spermine could be a mediator of dysfunctional maturation of DCs.
Altered maturation of peripheral blood dendritic cells in patients with breast cancer / S. Della Bella, M. Gennaro, M. Vaccari, C. Ferraris, S. Nicola, A. Riva, M. Clerici, M. Greco, M.L. Villa. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - 89:8(2003), pp. 1463-1472.
|Titolo:||Altered maturation of peripheral blood dendritic cells in patients with breast cancer|
DELLA BELLA, SILVIA ANGELA MARIA (Primo)
VILLA, MARIA LUISA (Ultimo)
|Parole Chiave:||Cell surface molecules; Cytokines; Dendritic cells; Tumour immunity|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore MED/06 - Oncologia Medica
|Data di pubblicazione:||2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/sj.bjc.6601243|
|Appare nelle tipologie:||01 - Articolo su periodico|