Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma

BACKGROUND: We previously reported that Trastuzumab-and Cetuximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) in cancer patients was impaired in comparison with that in healthy donors because of NK-cell dysfunction. In this study, we evaluated whether IL-21 could improve the impairment of ADCC in patients with oesophageal squamous cell carcinoma (ESCC), as IL-21 was reported to have the ability to activate NK cells. METHODS: We examined Trastuzumab-and Cetuximab-mediated ADCC of peripheral blood mononuclear cells (PBMCs) or of enriched NK cells derived from ESCC patients (n = 20) and healthy donors (n = 16) in the presence of IL-21. We further analysed ADCC-related molecules (perforin, granzyme-B, and CD247) on NK cells in response to IL-21. RESULTS: Trastuzumab-and Cetuximab-mediated ADCC of PBMCs or of enriched NK cells was enhanced by the addition of IL-21 in a dose-dependent manner and the levels of ADCC enhanced by IL-21 in patients were high enough in comparison with those in healthy donors, paralleling the upregulation of CD247 on NK cells. CONCLUSION: IL-21 could efficiently restore impaired ADCC in ESCC patients with the upregulation of CD247 molecules. British Journal of Cancer (2010) 102, 520-529. doi:10.1038/sj.bjc.6605502 www.bjcancer.com Published online 22 December 2009 (C) 2010 Cancer Research UK