title: Assessment of the change in cetuximab-induced antibody-dependent cellular cytotoxicity activity of natural killer cells by steroid.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR)-targeted therapy has been widely accepted as a promising treatment for solid tumors. Steroid treatment is used to prevent adverse effect of anti-EGFR antibody; however, influence of steroids in the antitumor activity of targeted antibody remains poorly understood. Herein, we demonstrated the impact of steroids in induced antibody-dependent cellular cytotoxicity (ADCC) activity of natural killer (NK) cells by cetuximab.
  
  
  METHODS
  Various numbers of NK cells from healthy donors were co-cultured with tumor and/or cetuximab with or without dexamethasone. After incubation, NK cells, ADCC activity, survival, and activation markers expression were determined.
  
  
  RESULTS
  Clinical concentration of dexamethasone treatment clearly inhibited cetuximab-induced ADCC activity of NK cells against head and neck squamous cell carcinoma (HNSCC) and colon cancer. Dexamethasone decreased the activation marker CD69 expression on NK cells.
  
  
  CONCLUSIONS
  This is the first report that shows the negative affect of steroids in cancer treatment using therapeutic antibody. Attention needs to be paid for using steroids in tumor treatment.
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.|Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kumai
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oikawa
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Aoki
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects* / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D000068818:Cetuximab / Q000494:pharmacology*; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000970:Antineoplastic Agents; D000068818:Cetuximab; D003907:Dexamethasone; D005938:Glucocorticoids; D037181:Lectins, C-Type; D000099192:CD69 Antigens
keywords: antibody-dependent cellular cytotoxicity (ADCC); cetuximab; head and neck squamous cell carcinoma (HNSCC); natural killer (NK) cells; steroid