• Open Access

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: Possible involvement of c-myc suppression by interferon-γin situ

Authors

  • Kazuyuki Matsushita,

    Corresponding author
    1. Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677,
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  • Toshinao Takenouchi,

    1. Division of Surgical Pathology, Chiba Cancer Center, 666-2 Nitoana, Chuoh-ku, Chiba 260-8717, and
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  • Hideaki Shimada,

    1. Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677,
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    • 4

      Equal contribution to this study.

  • Takeshi Tomonaga,

    1. Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677, Japan
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    • 4

      Equal contribution to this study.

  • Hideki Hayashi,

    1. Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677,
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  • Ayumi Shioya,

    1. Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677,
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  • Aki Komatsu,

    1. Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677,
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  • Hisahiro Matsubara,

    1. Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677,
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  • Takenori Ochiai

    1. Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677,
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To whom correspondence should be addressed. E-mail: kmatsu@faculty.chiba-u.jp

Abstract

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunological point of view, HLA-DR antigen, induced by interferon (IFN)-γ, is required for tumor-associated antigen recognition by CD4+ T cells. For instance, as reported previously, the expression of HLA-DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN-γ mRNA in the tissue. From another aspect, IFN-γ has been revealed to suppress c-myc expression in vivo through a stat1-dependent mechanism, which is important for cell growth, cell cycle and chromosome instability. In the present study, strong HLA-DR-positive expression on cancer cells was significantly related to better prognosis for colorectal cancer patients. High IFN-γ mRNA expression in situ indicated significantly less activation of c-myc mRNA expression. Further, HLA-DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long-term survival by multivariate analysis. Taken together, IFN-γ, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunological mechanism involved in the better long-term survival of colorectal cancer patients. (Cancer Sci 2006; 97: 57– 63)

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