Vaccination with CD133+ melanoma induces specific Th17 and Th1 cell–mediated antitumor reactivity against parental tumor

Accumulating evidence suggests that cancer cells possess a small subpopulation that survives during potentially lethal stresses, including chemotherapy, radiation treatment, and molecular-targeting therapy. CD133 is a putative marker that distinguishes a minor subpopulation from normal differentiated tumor cells in many cancers. Although it is necessary to eradicate all cancer cells to obtain a cure, effective treatment to eliminate the CD133+ treatment–tolerant cells has not been elucidated. In this study, we demonstrated that a CD133+ subpopulation in murine melanoma is immunogenic and that effector T cells specific for the CD133+ melanoma cells mediated potent antitumor reactivity, curing the mice of the parental melanoma. CD133+ melanoma antigens preferentially induced type 17 T helper (Th17) cells and Th1 cells but not Th2 cells. CD133+ melanoma cell–specific CD4+ T-cell treatment eradicated not only CD133+ tumor cells but also CD133− tumor cells while inducing long-lasting accumulation of lymphocytes and dendritic cells with upregulated MHC class II in tumor tissues. Further, the treatment prevented regulatory T-cell induction. These results indicate that T-cell immunotherapy is a promising treatment option to eradicate CD133+ drug-tolerant cells to obtain a cure for cancer.