Gedye Craig, Quirk Juliet, Browning Judy, Svobodová Suzanne, John Thomas, Sluka Pavel, Dunbar P Rod, Corbeil Denis, Cebon Jonathan, Davis Ian D
Ludwig Institute for Cancer Research, Austin Hospital, Studley Road, Heidelberg, VIC, 3084, Australia.
Cancer Immunol Immunother. 2009 Oct;58(10):1635-46. doi: 10.1007/s00262-009-0672-0. Epub 2009 Feb 17.
"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.
抵抗传统治疗的“癌症干细胞”可能是黑色素瘤治疗失败的一个原因。我们报告了一群克隆形成性黑色素瘤细胞亚群,其特征是在黑色素瘤和黑色素瘤细胞系中高表达prominin-1/CD133。这些细胞在体外具有增强的克隆形成能力和自我更新能力,并作为黑色素瘤干细胞的有限体外模型。在某些情况下,克隆形成性CD133(+)黑色素瘤细胞显示出一些癌胚(CT)抗原的表达增加。NY-ESO-1在一个表达HLA-A2的细胞系中的表达,使得CD133(+)克隆形成性黑色素瘤细胞在体外能够被NY-ESO-1特异性CD8(+) T淋巴细胞靶向杀伤。我们的体外研究结果提出了一个假设,即如果黑色素瘤干细胞在体内表达CT抗原,那么对这些抗原进行免疫靶向可能是黑色素瘤辅助治疗的一种可行临床策略。