Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis

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 th...

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Hauptverfasser: Toma, Marieta (VerfasserIn) , Wehner-Joachim, Rebekka (VerfasserIn) , Kloß, Anja (VerfasserIn) , Hübner, Linda (VerfasserIn) , Fodelianaki, Georgia (VerfasserIn) , Erdmann, Kati (VerfasserIn) , Füssel, Susanne (VerfasserIn) , Zastrow, Stefan (VerfasserIn) , Meinhardt, Matthias (VerfasserIn) , Seliger, Barbara (VerfasserIn) , Brech, Dorothee (VerfasserIn) , Noessner, Elfriede (VerfasserIn) , Tonn, Torsten (VerfasserIn) , Schäkel, Knut (VerfasserIn) , Bornhäuser, Martin (VerfasserIn) , Bachmann, Michael (VerfasserIn) , Wirth, Manfred (VerfasserIn) , Baretton, Gustavo Bruno (VerfasserIn) , Schmitz, Marc (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 02 Mar 2015
In: OncoImmunology
Year: 2015, Jahrgang: 4, Heft: 6, Pages: 1-14
ISSN:2162-402X
DOI:10.1080/2162402X.2015.1008342
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1080/2162402X.2015.1008342
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Verfasserangaben:Marieta Toma, Rebekka Wehner, Anja Kloß, Linda Hübner, Georgia Fodelianaki, Kati Erdmann, Susanne Füssel, Stefan Zastrow, Matthias Meinhardt, Barbara Seliger, Dorothee Brech, Elfriede Noessner, Torsten Tonn, Knut Schäkel, Martin Bornhäuser, Michael P. Bachmann, Manfred P. Wirth, Gustavo Baretton, and Marc Schmitz

MARC

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520 |a 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. 
650 4 |a ccRCC, clear cell renal cell carcinoma 
650 4 |a CTLs, cytotoxic T cells 
650 4 |a DCs, dendritic cells 
650 4 |a dendritic cells 
650 4 |a FCS, fetal calf serum 
650 4 |a HLA, human leukocyte antigen 
650 4 |a IFNγ, interferonγ 
650 4 |a IL, interleukin 
650 4 |a ILT, immunoglobulin-like transcript 
650 4 |a LPS, lipopolysaccharide 
650 4 |a NK cells, natural killer cells 
650 4 |a PBMCs, peripheral blood mononuclear cells 
650 4 |a PMA, phorbol myristate acetate 
650 4 |a renal cell carcinoma 
650 4 |a slan, 6-sulfo LacNAc 
650 4 |a T cells 
650 4 |a Th1 cells, T helper type I cells 
650 4 |a TMAs, tissue microarrays 
650 4 |a TNF-α, tumor necrosis factor-α 
650 4 |a tumor immunology 
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