[Immunotherapy of head and neck cancer. Identification of a novel mechanism for anti-EGFR mAb anti-tumor effects].

The epidermal growth factor receptor (EGFR) is found to be overexpressed in nearly all squamous cell carcinomas of the head and neck (SCCHN). Monoclonal antibodies (mAbs) against EGFR are currently used to treat recurrent or metastatic disease; however, their mode of action is not fully understood. To investigate the immunological effects of anti-EGFR mAb, a three-dimensional spheroid model of EGFR-expressing SCCHN was generated and used to study the effect of anti-EGFR mAb on leukocyte migration towards tumors. The blockade of EGFR by anti-EGFR mAb in EGFR-overexpressing SCCHN cells led to differential expression (array) of several cytokines and chemokines, including the chemokine MCP-1/CCL-2. This was confirmed by quantitative PCR and ELISPOT analyses and shown to be functionally relevant by blocking experiments. These 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 contribute to the anti-tumor effects of anti-EGFR mAb in vivo.