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.
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Abbreviations
- CT:
-
Cancer/testis
- CTL:
-
Cytotoxic T-lymphocyte
- CSC:
-
Cancer stem cell
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Acknowledgments
CG was supported by a National Health and Medical Research Council of Australia (NHMRC) Postgraduate Medical Scholarship. IDD is supported by a Victorian Cancer Agency Clinical Researcher Fellowship and is an Honorary National Health and Medical Research Council (NHMRC) Practitioner Fellow. JC is supported by an NHMRC Practitioner Fellowship. This project received the support of the Harry J Lloyd Charitable Trust. Thanks to the melanoma patients attending the Ludwig/Austin Melanoma Clinic, Ken Field (ImmunoID) and Paula Stoddart (Miltenyi Biotec) for technical assistance, and Dr Mark Shackleton (Walter and Eliza Hall Institute) and Dr. Otavia Caballero, Dr. Andy Simpson and Dr. Lloyd Old (LICR New York) for helpful comments and advice.
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Gedye, C., Quirk, J., Browning, J. et al. Cancer/testis antigens can be immunological targets in clonogenic CD133+ melanoma cells. Cancer Immunol Immunother 58, 1635–1646 (2009). https://doi.org/10.1007/s00262-009-0672-0
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DOI: https://doi.org/10.1007/s00262-009-0672-0