Cancer/testis antigens can be immunological targets in clonogenic CD133+ melanoma cells

Cancer Immunol Immunother. 2009 Oct;58(10):1635-46. doi: 10.1007/s00262-009-0672-0. Epub 2009 Feb 17.

Abstract

"Cancer stem cells" that resist conventional treatments may be a cause of therapeutic failure in melanoma. We report a subpopulation of clonogenic melanoma cells that are characterized by high prominin-1/CD133 expression in melanoma and melanoma cell lines. These cells have enhanced clonogenicity and self-renewal in vitro, and serve as a limited in vitro model for melanoma stem cells. In some cases clonogenic CD133(+) melanoma cells show increased expression of some cancer/testis (CT) antigens. The expression of NY-ESO-1 in an HLA-A2 expressing cell line allowed CD133(+) clonogenic melanoma cells to be targeted for killing in vitro by NY-ESO-1-specific CD8(+) T-lymphocytes. Our in vitro findings raise the hypothesis that if melanoma stem cells express CT antigens in vivo that immune targeting of these antigens may be a viable clinical strategy for the adjuvant treatment of melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Antigens, CD / metabolism*
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / therapeutic use*
  • Colony-Forming Units Assay
  • Cytotoxicity, Immunologic
  • Fluorescent Antibody Technique
  • Glycoproteins / metabolism*
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Melanoma / immunology*
  • Melanoma / secondary
  • Melanoma / therapy
  • Membrane Proteins / immunology*
  • Peptide Fragments / immunology
  • Peptides / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Glycoproteins
  • HLA-A2 Antigen
  • Membrane Proteins
  • PROM1 protein, human
  • Peptide Fragments
  • Peptides
  • RNA, Messenger