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2015 ; 15
(ä): 1009
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Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced
inhibition of dendritic cell differentiation
#MMPMID26704308
Grange C
; Tapparo M
; Tritta S
; Deregibus MC
; Battaglia A
; Gontero P
; Frea B
; Camussi G
BMC Cancer
2015[Dec]; 15
(ä): 1009
PMID26704308
show ga
BACKGROUND: Tumor immune-escape has been related to the ability of cancer cells
to inhibit T cell activation and dendritic cell (DC) differentiation. We
previously identified a tumor initiating population, expressing the mesenchymal
marker CD105, which fulfills the criteria for definition as cancer stem cells
(CD105(+) CSCs) able to release extracellular vesicles (EVs) that favor tumor
progression and metastases. The aim of the present study was to compare the
ability of renal CSCs and derived EVs to modulate the behavior of
monocyte-derived DCs with a non-tumor initiating renal cancer cell population
(CD105(-) TCs) and their EVs. METHODS: Maturation of monocyte-derived DCs was
studied in presence of CD105(+) CSCs and CD105(-) TCs and their derived EVs. DC
differentiation experiments were evaluated by cytofluorimetric analysis. T cell
proliferation and ELISA assays were performed. Monocytes and T cells were
purified from peripheral blood mononuclear cells obtained from healthy donors.
RESULTS: The results obtained demonstrate that both CD105(+) CSCs and CD105(-)
TCs impaired the differentiation process of DCs from monocytes. However, the
immune-modulatory effect of CD105(+) CSCs was significantly greater than that of
CD105(-) TCs. EVs derived from CD105(+) CSCs and in less extent, those derived
from CD105(-) TCs retained the ability to impair monocyte maturation and T cell
activation. The mechanism has been mainly related to the expression of HLA-G by
tumor cells and to its release in a form associated to EVs. HLA-G blockade
significantly reduced the inhibitory effect of EVs on DC differentiation.
CONCLUSIONS: In conclusion, the results of the present study indicate that renal
cancer cells and in particular CSCs and derived EVs impair maturation of DCs and
T cell immune response by a mechanism involving HLA-G.