Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma

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  • MASAKI Ayako
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences
  • ISHIDA Takashi
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • MAEDA Yasuhiro
    Laboratory of Hospital Pharmacy, Nagoya City University Graduate School of Pharmaceutical Sciences
  • SUZUKI Susumu
    Department of Tumor Immunology, Aichi Medical University School of Medicine
  • ITO Asahi
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • TAKINO Hisashi
    Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences
  • TOTANI Haruhito
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • YOSHIDA Takashi
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • KINOSHITA Shiori
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • OGURA Hiroka
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • NARITA Tomoko
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • RI Masaki
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • KUSUMOTO Shigeru
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • INAGAKI Atsushi
    Department of Hematology and Oncology, Nagoya City West Medical Center
  • KOMATSU Hirokazu
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
  • NIIMI Akio
    Department of Respiratory Medicine, Allergy and Rheumatology, Nagoya City University Graduate School of Medical Sciences
  • UEDA Ryuzo
    Department of Tumor Immunology, Aichi Medical University School of Medicine
  • UTSUNOMIYA Atae
    Department of Hematology, Imamura Bun-in Hospital
  • INAGAKI Hiroshi
    Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences
  • IIDA Shinsuke
    Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences

Bibliographic Information

Other Title
  • 成人T細胞白血病/リンパ腫におけるトリプトファン代謝の予後に関する意義
  • セイジン Tサイボウ ハッケツビョウ/リンパシュ ニ オケル トリプトファン タイシャ ノ ヨゴ ニ カンスル イギ

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Abstract

Purpose: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, and is an important micro-environmental factor suppressing antitumor immune responses. We investigated the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL). Experimental Design: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteers. The relationships between various clinical parameters were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients.  Results: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than in healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. There were no significant differences in serum Trp concentrations between ATL patients, HTLV-1 ACs and controls. IDO was possibly produced by ATL and/or cells in the microenvironment. Multivariate analyses demonstrated a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, to be significant independent detrimental prognostic factors in ATL and aggressive variant ATL.  Conclusions: Quantification of serum Kyn and Trp is prognostically useful for individual ATL patients. Furthermore, ATL is an appropriate disease for testing novel cancer immunotherapies targeting IDO.

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 56 (11), 2295-2304, 2015

    The Japanese Society of Hematology

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