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

摘要

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.