Natural killer cells kill human melanoma cells with characteristics of cancer stem cells

Int Immunol. 2009 Jul;21(7):793-801. doi: 10.1093/intimm/dxp047. Epub 2009 Jun 2.


Experimental and clinical data suggest that tumours harbour a cell population retaining stem cell characteristics that can drive tumorigenesis. CD133 is considered an important cancer stem cells (CSC)-associated marker. In a large variety of human malignancies, including melanoma, CD133(+) cells have been reported to comprise CSC. In this study, we show that melanoma cell lines are highly heterogeneous for the expression of several stem cell-associated markers including CD133, c-kit/CD117 and p75 neurotrophin receptor/CD271. Since no information is available on the ability of NK cells to recognize and lyse melanoma stem cells, we assessed whether melanoma cell lines, characterized by stem cell-like features, were susceptible to lysis by IL-2-activated NK cells. We show that activated NK cells efficiently kill malignant melanoma cell lines that were enriched in putative CSC by the use of different selection methods (i.e. CD133 expression, radioresistance or the ability to form melanospheres in stem cell-supportive medium). NK cell-mediated recognition and lysis of melanoma cells involved different combinations of activating NK receptors. Since CSC have been reported to be both drug resistant and radioresistant, our present data suggest that NK-based adoptive immunotherapy could represent a novel therapeutic approach to possibly eradicate metastatic melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Caspase 3 / immunology
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic*
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Humans
  • Immunotherapy, Adoptive
  • Interleukin-2 / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Melanoma / immunology*
  • Melanoma / therapy
  • Neoplastic Stem Cells / immunology*
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism
  • Peptides / immunology
  • Peptides / metabolism
  • Proto-Oncogene Proteins c-kit / immunology
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptors, Nerve Growth Factor / immunology
  • Receptors, Nerve Growth Factor / metabolism
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / therapy
  • Tumor Cells, Cultured


  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • IL2 protein, human
  • Interleukin-2
  • NGFR protein, human
  • Nerve Tissue Proteins
  • PROM1 protein, human
  • Peptides
  • Receptors, Nerve Growth Factor
  • Proto-Oncogene Proteins c-kit
  • Caspase 3