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Toma, M.* ; Wehner, R.* ; Kloss, A.* ; Huebner, L.* ; Fodelianaki, G.* ; Erdmann, K.* ; Fuessel, S.* ; Zastrow, S.* ; Meinhardt, M.* ; Seliger, B.* ; Brech, D. ; Nößner, E. ; Tonn, T.* ; Schaekel, K.* ; Bornhaeuser, M.* ; Bachmann, M.P.* ; Wirth, M.P.* ; Baretton, G.* ; Schmitz, M.*

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

OncoImmunology 4:e1008342 (2015)
DOI PMC
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dendritic Cells ; Renal Cell Carcinoma ; T Cells ; Tumor Immunology ; Tumor Microenvironment; Natural-killer-cells; Human Tumors; Antitumor Immunity; T-lymphocytes; Human Blood; Cancer; Responses; Immunotherapy; Cytotoxicity; Activation
Language english
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 2162-4011
e-ISSN 2162-402X
Journal OncoImmunology
Quellenangaben Volume: 4, Issue: 6, Pages: , Article Number: e1008342 Supplement: ,
Publisher Taylor & Francis
Publishing Place Philadelphia
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501700-001
DOI 10.1080/2162402X.2015.1008342
WOS ID WOS:000355203300006
Scopus ID 85053361483
Scopus ID 84944463340
PubMed ID 26155414
Erfassungsdatum 2015-06-19
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