Verteilung und Funktion verschiedener Subtypen dendritischer Zellen bei Nierenzellkarzinomen

Brauneck, Sven

dc.contributor.advisor	Middel, Peter PD Dr.
dc.contributor.author	Brauneck, Sven
dc.date.accessioned	2014-02-10T09:54:10Z
dc.date.available	2014-02-19T23:50:04Z
dc.date.issued	2014-02-10
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0022-5E1B-6
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-4328
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Verteilung und Funktion verschiedener Subtypen dendritischer Zellen bei Nierenzellkarzinomen	de
dc.type	doctoralThesis	de
dc.title.translated	Distribution and function of different dendritic cell subsets in renal cell carcinoma	de
dc.contributor.referee	Oppermann, Martin Prof. Dr.
dc.date.examination	2014-02-12
dc.description.abstracteng	Background: Renal cell carcinoma (RCC) represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs) in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking. Methods: We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated. Results: The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between CCL20 producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, CCL19 and CCL21 expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters. Conclusion: Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of CCL20 favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of CCL21 and CCL19 induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response.	de
dc.contributor.coReferee	Virsik-Köpp, Patricia Prof. Dr.
dc.subject.eng	dendritic cells	de
dc.subject.eng	rcc	de
dc.subject.eng	renal cell carcinoma	de
dc.subject.eng	vaccination	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5E1B-6-6
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.subject.gokfull	Pathologie / Pathologische Anatomie / Histopathologie / Zytopathologie - Allgemein- und Gesamtdarstellungen (PPN619875674)	de
dc.description.embargoed	2014-02-19
dc.identifier.ppn	778139948

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Human- und Zahnmedizin [2873]

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