Elimination of CD4+ T cells may overcome suppression of anti-HER2 immune responses in tumor-bearing hosts.

Abstract

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.

• Authors: Mikiya Ishihara, Isao Tawara, Lijie Wang, Yoshiyuki Takahashi, Hiroshi Shiku
• Journal: International journal of oncology (Int J Oncol) Vol. 22 Issue 5 Pg. 1135-9 (May 2003) ISSN: 1019-6439 [Print] Greece
• PMID: 12684682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• CD4 Antigens
• Receptor, ErbB-2

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• CD4 Antigens (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Female
• Fibrosarcoma (immunology)
• Immunosuppression Therapy
• Immunotherapy
• Lymphocyte Depletion
• Mice
• Mice, Inbred BALB C
• Receptor, ErbB-2 (immunology)
• Spleen (immunology)