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.

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.

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.

IL−21 could efficiently restore impaired ADCC in ESCC patients with the upregulation of CD247 molecules.

PMID: 20029417 [PubMed − indexed for MEDLINE] Source: National Library of Medicine.