Cetuximab is a IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR) used for the treatment of local advanced-head and neck squamous cell carcinoma (LA-HNSCC). A working mechanism of cetuximab include the ability to develop antibody-dependent cell-mediated cytotoxicity (ADCC), triggered by the interaction of the Fc portion of the antibody with the Fc receptor on the immune cell, mainly on Natural Killer (NK) cells. Invariant NKT (iNKT) cells play an important role in the activation of immune cell subset, including NK cells, and their deficiency is related to poor clinical outcome in LA-HNSCC. The aim of this work was to investigate the predictive role of ADCC and iNKT in LA-HNSCC patients treated with cetuximab-based therapy.
Twenty-eight LA-HNSCC patients treated with curative intent with cetuximab-based radio-chemotherapy were analysed. Peripheral blood samples were collected at start of therapy. ADCC was evaluated as ex vivo NK-dependent activity measuring LDH release as previously standardized in our laboratory. EGFR tumoral expression was analyzed by immunohistochemistry.
ADCC activity above the median value (high) correlated with a better OS as compared to ADCC below the median (low) in LA-HNSCC (p = 0.033). We observed a correlation also between high ADCC and response rate (p = 0.038). By univariate analysis on OS there were ADCC activity tumor size and HPV status as significant pronostic indicators. According to multivariate log-rank analysis only ADCC remained a significant predictor for OS (p = 0.03). If we stratified the EGFR 3+ patients into high and low ADCC performers, we observed an impressive increased OS in those with high ADCC (p = 0.024). iNKT cells number didn't significantly correlate with OS: nonetheless, we observed a trend to a longer survival after 10 months in patients with high iNKT cells (above the median values).
ADCC has a strong predictive value of cetuximab response in HNSCC. High tumoral EGFR expression and high ADCC confer a particularly long overall survival and suggest to combine this two biomarkers in order to predict clinical outcome in cetuximab-treated HNSCC patients.
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M.C. Merlano: Consultant for Merck Serono. All other authors have declared no conflicts of interest.