gms | German Medical Science

76. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

04.05. - 08.05.2005, Erfurt

Immuntolerance by regulation of migration and cytokine production of myeloid dendritic cells (MDC) by head and neck cancer (HNSCC)

Meeting Abstract

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  • corresponding author Carsten Brocks - Universitätsklinikum Schleswig Holstein, Campus Lübeck, Klinik für HNO, Lübeck
  • Henning Frenzel - Universitätsklinikum Schleswig Holstein, Campus Lübeck, Klinik für HNO, Lübeck
  • Ralph Pries - Universitätsklinikum Schleswig Holstein, Campus Lübeck, Klinik für HNO, Lübeck
  • Barbara Wollenberg - Universitätsklinikum Schleswig Holstein, Campus Lübeck, Klinik für HNO, Lübeck

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 76. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.. Erfurt, 04.-08.05.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc05hno471

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hno2005/05hno149.shtml

Veröffentlicht: 22. September 2005

© 2005 Brocks et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: Dendritic cells are professional antigen presenting cells with characteristic functions in humans. We focussed on myeloid dendritic cells, which activated by various stimuli migrate to locoregional lymph nodes to present peripheral antigens to T cells. Inactive MDC also migrate from healthy tissue to the lymphatic nodes and maintain immuntolerance.

In this study we examined migration behaviour and cytokine production of MDC under tumor microenvironment and stimulation with CpG-ODN.

Methods: Human MDC were isolated from PBMC using specific magnetic beat labeled antibodies (BDCA-1 isolation kit, Miltenyi).

Isolated MDC were co-incubated with HNSCC culture supernatant (for 2, 4, 8 or 12 hours ) and/or stimulated with CpG-ODN 2216 for 2 hours respectively. DMEM-Medium was used as a control. Incubated MDC were allowed to migrate through a membran against MIP 1ß (macrophage inflammatoric protein) (migrationassay, ChemoTx System™, NeuroProbe).

The expression of CD11c, lin-package and HLA-DR, CD40, CD69, CD80, CD83, CD86 were determined by flow cytometry. Cytokine secretion (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, GM-CSF, INF and TNF) was detected by ELISA and Bioplex.

Results: HNSCC incubated MDC migrate significantly better compared to medium control. Activation of MDC by CpG-ODN resulted in a decreased migration of MDC. The migration of MDC induced by HNSCC is lowered but not completely inhibited by CpG. MDC are triggered by HNSCC to produce high levels of IL1 and IL-10 in a time-dependent manner.

Discussion: Initial data show that HNSCC increase MDC migration. As HNSCC do not benefit of presentation through MDC in the locoregional lymph node, we assumed an immuno escape mechanism: HNSCC induce production of high levels of immunosuppressive IL-10 and HNSCC proliferation inducing IL-1 in MDC. Activation of MDC by CpG can reduce but no inhibit the production of IL-10 by MDC. IL-1 production by MDC cannot be affected by CpG.

Our results show a significant time dependent HNSCC caused suppression of MDC activation and migration. HNSCC are able to send MDC with an altered immunotolerating message towards lymphatic nodes.

This project is supported by a grant of Mildred-Scheel-Stiftung (Deutsche Krebshilfe) 10-2074-Wo2