The critical role of Th1-dominant immunity in tumor immunology.
To investigate the precise role of antigen-specific Th1 and Th2 cells in tumor immunity, we developed a novel adoptive tumor-immunotherapy model using OVA-specific Th1 and Th2 cells and an OVA gene-transfected tumor. This therapeutic model demonstrated that both antigen-specific Th1 and Th2 cells had strong antitumor activity in vivo with distinct mechanisms. However, immunological memory suitable for the generation of tumor-specific cytotoxic T lymphocytes was induced only when tumor-bearing mice received Th1 cell therapy, but not Th2 cell therapy. Thus it was strongly suggested that Th1-dominant immunity is critically important for the induction of antitumor cellular immunity in vivo. We also proposed that several immunomodulating protocols using interleukin (IL)-12, IL-12 gene, the natural killer T cell ligand alpha-galactosylceramide, or Th1 cytokine-conditioned dendritic cells might be useful strategies for the induction of Th1-dominant immunity essential for the development of tumor-specific immunotherapy.
Nishimura
T
T
Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. tak24@imm.hokudai.ac.jp
Nakui
M
M
Sato
M
M
Iwakabe
K
K
Kitamura
H
H
Sekimoto
M
M
Ohta
A
A
Koda
T
T
Nishimura
S
S
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D015316:Genetic Therapy; D007111:Immunity, Cellular / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D019496:Cancer Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D005699:Galactosylceramides; C002454:galactocerebroside; D018664:Interleukin-12; D010047:Ovalbumin