Assessment of the change in cetuximab-induced antibody-dependent cellular cytotoxicity activity of natural killer cells by steroid

Head Neck. 2016 Mar;38(3):410-6. doi: 10.1002/hed.23906. Epub 2015 May 26.

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.

Conclusion: 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.

Keywords: antibody-dependent cellular cytotoxicity (ADCC); cetuximab; head and neck squamous cell carcinoma (HNSCC); natural killer (NK) cells; steroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Cell Line, Tumor / drug effects
  • Cell Survival
  • Cetuximab / pharmacology*
  • Coculture Techniques
  • Dexamethasone / pharmacology*
  • Flow Cytometry
  • Glucocorticoids / pharmacology*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type / metabolism
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antineoplastic Agents
  • CD69 antigen
  • Glucocorticoids
  • Lectins, C-Type
  • Dexamethasone
  • Cetuximab