title: Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis.
abstract: 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.
authors.affiliation: Institute of Pathology; University Hospital of Dresden ; Dresden, Germany.
authors.forename: Marieta
authors.initials: M
authors.lastname: Toma
authors.affiliation: Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.affiliation: Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Kloß
authors.affiliation: Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Hübner
authors.affiliation: Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany ; Center for Regenerative Therapies Dresden ; Dresden, Germany.
authors.forename: Georgia
authors.initials: G
authors.lastname: Fodelianaki
authors.affiliation: Department of Urology; University Hospital of Dresden ; Dresden, Germany.
authors.forename: Kati
authors.initials: K
authors.lastname: Erdmann
authors.affiliation: Department of Urology; University Hospital of Dresden ; Dresden, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Füssel
authors.affiliation: Department of Urology; University Hospital of Dresden ; Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zastrow
authors.affiliation: Institute of Pathology; University Hospital of Dresden ; Dresden, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Meinhardt
authors.affiliation: Institute for Medical Immunology; Martin Luther University Halle-Wittenberg ; Halle (Saale), Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.affiliation: Institute of Molecular Immunology; Helmholtz Center Munich; German Research Center for Environmental Health Munich ; Munich, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Brech
authors.affiliation: Institute of Molecular Immunology; Helmholtz Center Munich; German Research Center for Environmental Health Munich ; Munich, Germany.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Noessner
authors.affiliation: Center for Regenerative Therapies Dresden ; Dresden, Germany ; German Red Cross Blood Service ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.affiliation: Department of Dermatology; University Hospital of Heidelberg ; Heidelberg, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Schäkel
authors.affiliation: Center for Regenerative Therapies Dresden ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany ; Department of Medicine I; University Hospital of Dresden ; Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Center for Regenerative Therapies Dresden ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany ; Department of Radioimmunology; Institute of Radiopharmaceutical Cancer Research; Helmholtz Center Dresden-Rossendorf ; Dresden, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bachmann
authors.affiliation: Department of Urology; University Hospital of Dresden ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany.
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Wirth
authors.affiliation: Institute of Pathology; University Hospital of Dresden ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baretton
authors.affiliation: Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany ; Center for Regenerative Therapies Dresden ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
keywords: CTLs, cytotoxic T cells; DCs, dendritic cells; FCS, fetal calf serum; HLA, human leukocyte antigen; IFNγ, interferonγ; IL, interleukin; ILT, immunoglobulin-like transcript; LPS, lipopolysaccharide; NK cells, natural killer cells; PBMCs, peripheral blood mononuclear cells; PMA, phorbol myristate acetate; T cells; TMAs, tissue microarrays; TNF-α, tumor necrosis factor-α; Th1 cells, T helper type I cells; ccRCC, clear cell renal cell carcinoma; dendritic cells; renal cell carcinoma; slan, 6-sulfo LacNAc; tumor immunology; tumor microenvironment