title: Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor.
abstract: 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.
authors.affiliation: Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Course for Biological Functions and Medical Control, Graduate School of Medical and Dental Sciences, Niigata University, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Miyabayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kagamu
authors.forename: Jun
authors.initials: J
authors.lastname: Koshio
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Junko
authors.initials: J
authors.lastname: Baba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Junta
authors.initials: J
authors.lastname: Tanaka
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D016233:Immunotherapy, Active / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods; D008285:Major Histocompatibility Complex; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse