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

Br J Cancer. 2010 Feb 2;102(3):520-9. doi: 10.1038/sj.bjc.6605502. Epub 2009 Dec 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Cell Line, Tumor
  • Cetuximab
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / immunology
  • Female
  • Humans
  • Interleukins / pharmacology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Receptors, Interleukin-21 / analysis


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukins
  • Receptors, Interleukin-21
  • interleukin-21
  • Cetuximab