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.


CONCLUSIONS
IL-21 could efficiently restore impaired ADCC in ESCC patients with the upregulation of CD247 molecules.
Watanabe
M
M
First Department of Surgery, University of Yamanashi, Yamanashi 409-3898, Japan.
Kono
K
K
Kawaguchi
Y
Y
Mizukami
Y
Y
Mimura
K
K
Maruyama
T
T
Fujii
H
H
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053655:Receptors, Interleukin-21 / Q000032:analysis; D000098546:Interleukin-21
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007378:Interleukins; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21; D000068818:Cetuximab