Elimination of CD4+ T cells may overcome suppression of anti-HER2 immune responses in tumor-bearing hosts.
In this study, we analyzed specific anti-tumor immune responses in tumor-bearing hosts by measuring HER2-specific CD8+ T cell responses. No measurable HER2-derived peptide (HER2p63)-specific CD8+ T cells were present in the spleens of mice in the early to late phase of tumor-bearing. Vaccination with HER2 protein and cholesteryl group-bearing pullulan (CHP-HER2 complex) induced HER2-specific CD8+ T cells, but their numbers continuously declined as tumors continued growing. Removal of CD4+ T cells by anti-CD4 monoclonal antibody in the early tumor-bearing stage resulted in tumor regression. The combination of CHP-HER2 complex vaccination and depletion of CD4+ T cells enhanced and restored HER2-specific CD8+ T cells in the late stage of tumor-bearing, and also suppressed tumor growth. These results indicate the importance of manipulation of CD4+ T cells in developing effective immunotherapies as cancer vaccines.
Ishihara
Mikiya
M
Second Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Tawara
Isao
I
Wang
Lijie
L
Takahashi
Yoshiyuki
Y
Shiku
Hiroshi
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology*; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D018719:Erb-b2 Receptor Tyrosine Kinases