title: Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations.
abstract: Tissue dendritic cells (DCs) may influence the progression of renal cell carcinoma (RCC) by regulating the functional capacity of antitumor effector cells. DCs and their interaction with T cells were analyzed in human RCC and control kidney tissues. The frequency of CD209(+) DCs in RCCs was found to be associated with an unfavorable T(H)1 cell balance in the tissue and advanced tumor stages. The CD209(+) DCs in RCC were unusual because most of them co-expressed macrophage markers (CD14, CD163). The phenotype of these enriched-in-renal-carcinoma DCs (ercDCs) could be reiterated in vitro by carcinoma-secreted factors (CXCL8/IL-8, IL-6, and vascular endothelial growth factor). ErcDCs resembled conventional DCs in costimulatory molecule expression and antigen cross-presentation. They did not suppress cognate cytotoxic T-lymphocyte function and did not cause CD3ζ down-regulation, FOXP3 induction, or T-cell apoptosis in situ or in vitro; thus, they are different from classic myeloid-derived suppressor cells. ErcDCs secreted high levels of metalloproteinase 9 and used T-cell crosstalk to increase tumor-promoting tumor necrosis factor α and reduce chemokines relevant for T(H)1-polarized lymphocyte recruitment. This modulation of the tumor environment exerted by ercDCs suggests an immunologic mechanism by which tumor control can fail without involving cytotoxic T-lymphocyte inhibition. Pharmacologic targeting of the deviated DC differentiation could improve the efficacy of immunotherapy against RCC.
authors.affiliation: Institute of Molecular Immunology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
authors.forename: Ainhoa-M
authors.initials: AM
authors.lastname: Figel
authors.forename: Dorothee
authors.initials: D
authors.lastname: Brech
authors.forename: Petra U
authors.initials: PU
authors.lastname: Prinz
authors.forename: Ulrike K
authors.initials: UK
authors.lastname: Lettenmeyer
authors.forename: Judith
authors.initials: J
authors.lastname: Eckl
authors.forename: Adriana
authors.initials: A
authors.lastname: Turqueti-Neves
authors.forename: Josef
authors.initials: J
authors.lastname: Mysliwietz
authors.forename: David
authors.initials: D
authors.lastname: Anz
authors.forename: Nicole
authors.initials: N
authors.lastname: Rieth
authors.forename: Niklas
authors.initials: N
authors.lastname: Muenchmeier
authors.forename: Alexander
authors.initials: A
authors.lastname: Buchner
authors.forename: Stefan
authors.initials: S
authors.lastname: Porubsky
authors.forename: Sabine I
authors.initials: SI
authors.lastname: Siegert
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Elfriede
authors.initials: E
authors.lastname: Noessner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D045142:Cross-Priming; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger