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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-53895

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; Noessner, E (2011). Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations. American Journal of Pathology, 179(1):436-451.

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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.

Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
DDC:570 Life sciences; biology
610 Medicine & health
Deposited On:09 Jan 2012 17:44
Last Modified:04 Dec 2013 14:11
Publisher DOI:10.1016/j.ajpath.2011.03.011
PubMed ID:21703422
Citations:Web of Science®. Times Cited: 10
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Scopus®. Citation Count: 11

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