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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncoimmunology
2015 ; 4
(6
): e1008342
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Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell
carcinoma is associated with poor prognosis
#MMPMID26155414
Toma M
; Wehner R
; Kloß A
; Hübner L
; Fodelianaki G
; Erdmann K
; Füssel S
; Zastrow S
; Meinhardt M
; Seliger B
; Brech D
; Noessner E
; Tonn T
; Schäkel K
; Bornhäuser M
; Bachmann MP
; Wirth MP
; Baretton G
; Schmitz M
Oncoimmunology
2015[Jun]; 4
(6
): e1008342
PMID26155414
show ga
Dendritic cells (DCs) essentially contribute to the induction and regulation of
innate and adaptive immunity. Based on these important properties, DCs may
profoundly influence tumor progression in patients. However, little is known
about the role of distinct human DC subsets in primary tumors and their impact on
clinical outcome. In the present study, we investigated the characteristics of
human 6-sulfo LacNAc (slan) DCs in clear cell renal cell carcinoma (ccRCC).
slanDCs have been shown to display various tumor-directed properties and to
accumulate in tumor-draining lymph nodes from patients. When evaluating 263 ccRCC
and 227 tumor-free tissue samples, we found increased frequencies of slanDCs in
ccRCC tissues compared to tumor-free tissues. slanDCs were also detectable in the
majority of 24 metastatic lymph nodes and 67 distant metastases from ccRCC
patients. Remarkably, a higher density of slanDCs was significantly associated
with a reduced progression-free, tumor-specific or overall survival of ccRCC
patients. Tumor-infiltrating slanDCs displayed an immature phenotype expressing
interleukin-10. ccRCC cells efficiently impaired slanDC-induced T-cell
proliferation and programming as well as natural killer (NK) cell activation. In
conclusion, these findings indicate that higher slanDC numbers in ccRCC tissues
are associated with poor prognosis. The induction of a tolerogenic phenotype in
slanDCs leading to an insufficient activation of innate and adaptive antitumor
immunity may represent a novel immune escape mechanism of ccRCC. These
observations may have implications for the design of therapeutic strategies that
harness tumor-directed functional properties of DCs against ccRCC.