CTLA-4+ regulatory T cells are increased in cetuximab treated head and neck cancer patients, suppress NK cell cytotoxicity and correlate with poor prognosis (TUM2P.916)

The EGFR-targeted antibody, cetuximab, is clinically effective against head and neck cancer (HNC) but only in 15 - 20% of patients. We hypothesized that regulatory T cells may have functional and clinical impact antitumor immunity induced in cetuximab-treated patients. Indeed, Treg frequency and expression of CTLA-4, CD39, and surface TGF-β were significantly increased after cetuximab-based therapy. These Treg were inversely associated with functional activity of intratumoral NK cells and with clinical outcome in cetuximab-treated HNC patients. Importantly, NK cells selectively eliminated intratumoral Treg in the presence of anti-CTLA mAb (ipilimumab), which overcame the Treg suppressive activity on cetuximab-mediated ADCC. These results suggest that differences in Treg-mediated suppression may play a role in the clinical response to cetuximab therapy, and that efficacy of cetuximab therapy could be enhanced by adding ipilimumab to eliminate Treg, thus promoting anti-tumor immunity.