PMID- 26155414 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210112 IS - 2162-4011 (Print) IS - 2162-402X (Electronic) IS - 2162-4011 (Linking) VI - 4 IP - 6 DP - 2015 Jun TI - Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis. PG - e1008342 LID - e1008342 AB - 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. FAU - Toma, Marieta AU - Toma M AD - Institute of Pathology; University Hospital of Dresden ; Dresden, Germany. FAU - Wehner, Rebekka AU - Wehner R AD - Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany. FAU - Kloss, Anja AU - Kloss A AD - Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany. FAU - Hubner, Linda AU - Hubner L AD - Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany. FAU - Fodelianaki, Georgia AU - Fodelianaki G AD - Institute of Immunology; Medical Faculty; TU Dresden ; Dresden, Germany ; Center for Regenerative Therapies Dresden ; Dresden, Germany. FAU - Erdmann, Kati AU - Erdmann K AD - Department of Urology; University Hospital of Dresden ; Dresden, Germany. FAU - Fussel, Susanne AU - Fussel S AD - Department of Urology; University Hospital of Dresden ; Dresden, Germany. FAU - Zastrow, Stefan AU - Zastrow S AD - Department of Urology; University Hospital of Dresden ; Dresden, Germany. FAU - Meinhardt, Matthias AU - Meinhardt M AD - Institute of Pathology; University Hospital of Dresden ; Dresden, Germany. FAU - Seliger, Barbara AU - Seliger B AD - Institute for Medical Immunology; Martin Luther University Halle-Wittenberg ; Halle (Saale), Germany. FAU - Brech, Dorothee AU - Brech D AD - Institute of Molecular Immunology; Helmholtz Center Munich; German Research Center for Environmental Health Munich ; Munich, Germany. FAU - Noessner, Elfriede AU - Noessner E AD - Institute of Molecular Immunology; Helmholtz Center Munich; German Research Center for Environmental Health Munich ; Munich, Germany. FAU - Tonn, Torsten AU - Tonn T AD - 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. FAU - Schakel, Knut AU - Schakel K AD - Department of Dermatology; University Hospital of Heidelberg ; Heidelberg, Germany. FAU - Bornhauser, Martin AU - Bornhauser M AD - 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. FAU - Bachmann, Michael P AU - Bachmann MP AD - 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. FAU - Wirth, Manfred P AU - Wirth MP AD - Department of Urology; University Hospital of Dresden ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany. FAU - Baretton, Gustavo AU - Baretton G AD - Institute of Pathology; University Hospital of Dresden ; Dresden, Germany ; German Cancer Consortium (DKTK) ; Dresden, Germany ; German Cancer Research Center (DKFZ) ; Heidelberg, Germany. FAU - Schmitz, Marc AU - Schmitz M AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150302 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 PMC - PMC4485722 OTO - NOTNLM OT - CTLs, cytotoxic T cells OT - DCs, dendritic cells OT - FCS, fetal calf serum OT - HLA, human leukocyte antigen OT - IFNgamma, interferongamma OT - IL, interleukin OT - ILT, immunoglobulin-like transcript OT - LPS, lipopolysaccharide OT - NK cells, natural killer cells OT - PBMCs, peripheral blood mononuclear cells OT - PMA, phorbol myristate acetate OT - T cells OT - TMAs, tissue microarrays OT - TNF-alpha, tumor necrosis factor-alpha OT - Th1 cells, T helper type I cells OT - ccRCC, clear cell renal cell carcinoma OT - dendritic cells OT - renal cell carcinoma OT - slan, 6-sulfo LacNAc OT - tumor immunology OT - tumor microenvironment EDAT- 2015/07/15 06:00 MHDA- 2015/07/15 06:01 PMCR- 2016/03/02 CRDT- 2015/07/09 06:00 PHST- 2014/11/17 00:00 [received] PHST- 2015/01/07 00:00 [revised] PHST- 2015/01/08 00:00 [accepted] PHST- 2015/07/09 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2015/07/15 06:01 [medline] PHST- 2016/03/02 00:00 [pmc-release] AID - 1008342 [pii] AID - 10.1080/2162402X.2015.1008342 [doi] PST - epublish SO - Oncoimmunology. 2015 Mar 2;4(6):e1008342. doi: 10.1080/2162402X.2015.1008342. eCollection 2015 Jun.