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

摘要: Overexpression of the epidermal growth factor receptor (EGFR) is a hallmark squamous cell carcinoma head and neck (SCCHN). Monoclonal antibodies (mAbs) against EGFR are currently used for therapy recurrent or metastatic disease; however, their mode action not completely understood. To investigate immunological effects anti-EGFR mAb, we generated three-dimensional spheroid model EGFR-expressing SCCHN this to study effect mAb on leukocyte migration toward tumors. Pretreatment with blocking EMD 72000, its F(ab′)2 fragments an tyrosine kinase inhibitor led substantially increased infiltration into overexpressing tumor spheroids, but those low expression. Nonblocking fibroblast-specific did affect infiltration, suggesting that observed increase in depends interference activation. Using human cytokine macroarray, demonstrated blockade by EGFR-overexpressing cells leads differential expression several cytokines chemokines, including chemokine MCP-1/CCL-2. The significant upregulation MCP-1/CCL2 exposure was confirmed quantitative PCR enzyme-linked immunospot analyses. Moreover, anti-MCP-1 antibody inhibited induced pointing important role mAb-induced migration. Our findings demonstrate induces spheroids upregulating This novel mechanism may contribute antitumor vivo. © 2009 Wiley-Liss, Inc.