title: Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells.
abstract: CD8(+) CTLs play a critical role in antitumor immunity. However, vaccination with synthetic peptide containing CTL epitopes has not been generally effective in inducing protective antitumor immunity. In this study, we addressed the detailed mechanism(s) involved in this failure using a new tumor model of BALB/c transplanted tumors expressing NY-ESO-1, an extensively studied human cancer/testis Ag. Whereas peptide immunization with an H2-D(d)-restricted CTL epitope derived from NY-ESO-1 (NY-ESO-1 p81-88) induced NY-ESO-1(81-88)-specific CD8(+) T cells in draining lymph nodes and spleens, tumor growth was significantly enhanced. Single-cell analysis of specific CD8(+) T cells revealed that peptide immunization caused apoptosis of >80% of NY-ESO-1(81-88)-specific CD8(+) T cells at tumor sites and repetitive immunization further diminished the number of specific CD8(+) T cells. This phenomenon was associated with elevated surface expression of Fas and programmed death-1. When peptide vaccination was combined with an adjuvant, a TLR9 ligand CpG, the elevated Fas and programmed death-1 expression and apoptosis induction were not observed, and vaccine with peptide and CpG was associated with strong tumor growth inhibition. Selection of appropriate adjuvants is essential for development of effective cancer vaccines, with protection of effector T cells from peptide vaccine-induced apoptosis being a prime objective.
authors: Department of Cancer Vaccine, Mie University Graduate School of Medicine, Mie, Japan.
authors: Daisuke
authors: D
authors: Muraoka
authors: Takuma
authors: T
authors: Kato
authors: Linan
authors: L
authors: Wang
authors: Yuka
authors: Y
authors: Maeda
authors: Takuro
authors: T
authors: Noguchi
authors: Naozumi
authors: N
authors: Harada
authors: Kazuyoshi
authors: K
authors: Takeda
authors: Hideo
authors: H
authors: Yagita
authors: Philippe
authors: P
authors: Guillaume
authors: Immanuel
authors: I
authors: Luescher
authors: Lloyd J
authors: LJ
authors: Old
authors: Hiroshi
authors: H
authors: Shiku
authors: Hiroyoshi
authors: H
authors: Nishikawa
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D019470:Biolistics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology; D007279:Injections, Subcutaneous; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000473:pathology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins; D022223:Vaccines, Subunit