gms | German Medical Science

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.