Expansion of CD16 positive and negative human NK cells in response to tumor stimulation

Eur J Immunol. 2014 May;44(5):1517-25. doi: 10.1002/eji.201344170. Epub 2014 Feb 20.

Abstract

NK cells are innate immune lymphocytes that express a vast repertoire of germ-line encoded receptors for target recognition. These receptors include inhibitory and activating proteins, among the latter of which is CD16, a low affinity binding Fc receptor. Here, we show that human NK cells expand in response to stimulation with various tumor cell lines. We further demonstrate that the tumor-derived expansion of NK cells is accompanied by rapid, cell-dependent, changes in CD16 expression levels. We show that in NK cells expanded in response to the EBV-transformed cell line 721.221, CD16 is shed and therefore approximately half of the expanded 721.221-derived NK-cell population does not express CD16. We also show, in contrast, that in response to 1106mel cells, CD16 expression is maintained on the cell surface of the expanded NK cells due to an antibody-dependent mechanism. Our results may provide a basis for the selective expansion of NK cells that may be used for tumor immunotherapy.

Keywords: Antibodies; CD16; NK-cell-expansion; human NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neoplasm / immunology*
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Coculture Techniques
  • Female
  • GPI-Linked Proteins / biosynthesis
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunotherapy
  • Killer Cells, Natural
  • Male
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Receptors, IgG / biosynthesis
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology*

Substances

  • Antibodies, Neoplasm
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Receptors, IgG