gms | German Medical Science

78. 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.

16.05. - 20.05.2007, München

A novel mechanism for anti-EGFR antibody action involves chemokine-mediated leukocyte infiltration

Meeting Abstract

  • corresponding author Thomas K. Hoffmann - Dept. of Otorhinolaryngology, Duesseldorf, Germany
  • Kerstin Schirlau - Dept. of Otorhinolaryngology, Duesseldorf, Germany
  • Vera Balz - Dept. of Otorhinolaryngology, Duesseldorf, Germany
  • Torsten Reichert - Dept. of Maxillofacial Surgery, Regensburg, Germany
  • Murat Bas - Dept. of Otorhinolaryngology, Duesseldorf, Germany
  • Theresa L. Whiteside - Hillman Cancer Center, Pittsburgh, United States

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. 78th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. Munich, 16.-20.05.2007. Düsseldorf, Köln: German Medical Science; 2007. Doc07hno084

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hno2007/07hno084.shtml

Veröffentlicht: 8. August 2007

© 2007 Hoffmann 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

Overexpression of the epidermal growth factor receptor (EGFR) is a hallmark of squamous cell carcinoma of the head and neck (SCCHN). Monoclonal antibodies (mAbs) against EGFR are considered for the therapy of recurrent or metastatic disease; however, their mode of action is incompletely understood.

To investigate the immunological effects of anti-EGFR mAb, we generated a three-dimensional spheroid model of EGFR-expressing SCCHN and used this model to study the effect of anti-EGFR mAb on leukocyte migration towards tumors. Pretreatment with the blocking anti-EGFR mAb EMD 72000 led to substantially increased leukocyte infiltration into EGFR overexpressing tumor spheroids, but not into those with low EGFR expression. Using a human cytokine macroarray, we demonstrated that the blockade of EGFR by anti-EGFR mAb in EGFR-overexpressing SCCHN cells leads to differential expression of several cytokines and chemokines, including the chemokine MCP-1/CCL-2. The significant up-regulation of MCP-1/CCL2 upon exposure to anti-EGFR mAb was confirmed by quantitative PCR and ELISPOT analyses. Moreover, blocking anti-MCP-1 antibody inhibited leukocyte migration towards tumor cells induced by anti-EGFR mAb, pointing to an important role of MCP-1/CCL2 in anti-EGFR mAb-induced leukocyte migration.

Our findings demonstrate that anti-EGFR mAb induces leukocyte infiltration to tumor spheroids by up-regulating chemokine expression. This novel mechanism for anti-EGFR mAb action may in part be responsible for the anti-tumor effects of anti-EGFR mAb in vivo.