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

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

Author information

1
First Department of Surgery, University of Yamanashi, Yamanashi 409-3898, Japan.

Abstract

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.

PMID:
20029417
PMCID:
PMC2822939
DOI:
10.1038/sj.bjc.6605502
[Indexed for MEDLINE]
Free PMC Article

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