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Figel, A.-M. ; Brech, D. ; Prinz, P.U. ; Lettenmeyer, U.K. ; Eckl, J. ; Turqueti-Neves, A. ; Mysliwietz, J. ; Anz, D.* ; Rieth, N.* ; Muenchmeier, N.* ; Buchner, A.* ; Porubsky, S.* ; Siegert, S.I.* ; Segerer, S.* ; Nelson, P.J.* ; Nößner, E.

Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations.

Am. J. Pathol. 179, 436-451 (2011)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords NATURAL-KILLER-CELLS; DC-SIGN CD209; ANTIGEN PRESENTATION; EXPRESSION; KIDNEY; DIFFERENTIATION; MACROPHAGES; HETEROGENEITY; ACTIVATION; SURVIVAL
ISSN (print) / ISBN 0002-9440
e-ISSN 1525-2191
Quellenangaben Volume: 179, Issue: 1, Pages: 436-451 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NJ
Reviewing status Peer reviewed