CD4 T Cell-Mediated Masking Effects of the Immunogenicity of Tumor-Associated Antigens are Qualitatively and Quantitatively Different Depending on the Individual Antigens

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  • Okano Shinji
    Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University
  • Matsumoto Yoshihiro
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • Yoshiya Shohei
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • Yamashita Yo-Ichi
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • Harimoto Norifumi
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • Ikegami Toru
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • Shirabe Ken
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • Harada Mamoru
    Department of Immunology, Shimane University Faculty of Medicine
  • Yoshikai Yasunobu
    Department of Infection Control, Medical Institute of Bioregulation, Kyushu University
  • Maehara Yoshihiko
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University

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Other Title
  • CD4 T細胞による腫瘍関連抗原の免疫原性の抑制効果は個々の抗原に依存して,質的量的な違いがある

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Description

The use of cancer immunotherapy as part of multidisciplinary therapies for cancer is a promising strategy for the cure of advanced cancer patients. In cancer immunotherapy, the effective priming of tumor-associated antigen (TAA)-specific CD8^+ T cells is essential, and therefore, the appropriate selection of the best peptide for targeting the cancer is a most important concern. One criticism in the selection of a TAA is the immunogenicity of the TAA, the vaccination of which effectively elicits clinical responses. However, the critical basic immunological factors that affect the differences in the immunogenicity of TAAs remain to be elucidated. Here we found that CD4 T-cell responses suppressed the immunogenicity of the concomitant TAA in a murine melanoma model in which intratumoral activated dendritic therapy (ITADT) was used for treatment of the established cancer, and we observed that the antitumor effects were largely dependent on the CD8 T-cell response. CD4 T-cell depletion simply enhanced the tyrosinase-related protein (TRP) -2_<180-188> peptide-specific cytotoxic T-cell (CTL) responses, and CD4 T-cell depletion provided immunogenicity for mgp100_<25-33> peptide, to which a CTL response could not be detected at all in CD4 T-cell-intact mice in the early therapeutic phase. Further, the mgp100_<25-33> peptide-specific CTL response again became undetectable after the recovery of CD4 T cells in previously CD4-depleted, tumor-eradicated mice, whereas the TRP-2_<180-188> peptide-specific CTL response was still much stronger in CD4-depleted mice than in CD4-intact mice. These findings suggest that the CD4 T cell-mediated masking effects of the immunogenicity of tumor-associated antigens are qualitatively and quantitatively different depending on the individual antigens.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 104 (1), 1-14, 2013-01-25

    Fukuoka Medical Association

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