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

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Author(s)

    • 正木 彩子 MASAKI Ayako
    • 名古屋市立大学医学部血液・腫瘍内科|名古屋市立大学医学部臨床病態病理学 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
    • 小椋 啓加 OGURA Hiroka
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 成田 朋子 [他] NARITA Tomoko
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 李 政樹 RI Masaki
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 楠本 茂 KUSUMOTO Shigeru
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 稲垣 淳 INAGAKI Atsushi
    • 名古屋市立西部医療センター血液内科 Department of Hematology and Oncology, Nagoya City West Medical Center
    • 小松 弘和 KOMATSU Hirokazu
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 新実 彰男 NIIMI Akio
    • 名古屋市立大学呼吸器・免疫アレルギー内科 Department of Respiratory Medicine, Allergy and Rheumatology, Nagoya City University Graduate School of Medical Sciences
    • 上田 龍三 UEDA Ryuzo
    • 愛知医科大学腫瘍免疫寄附講座 Department of Tumor Immunology, Aichi Medical University School of Medicine
    • 稲垣 宏 INAGAKI Hiroshi
    • 名古屋市立大学医学部臨床病態病理学 Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences
    • 石田 高司 ISHIDA Takashi
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 飯田 真介 IIDA Shinsuke
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 前田 康弘 MAEDA Yasuhiro
    • 名古屋市立大学薬学部病院薬剤学 Laboratory of Hospital Pharmacy, Nagoya City University Graduate School of Pharmaceutical Sciences
    • 鈴木 進 SUZUKI Susumu
    • 愛知医科大学腫瘍免疫寄附講座 Department of Tumor Immunology, Aichi Medical University School of Medicine
    • 伊藤 旭 ITO Asahi
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 滝野 寿 TAKINO Hisashi
    • 名古屋市立大学医学部臨床病態病理学 Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences
    • 戸谷 治仁 TOTANI Haruhito
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 吉田 嵩 YOSHIDA Takashi
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences
    • 木下 史緒理 KINOSHITA Shiori
    • 名古屋市立大学医学部血液・腫瘍内科 Department of Hematology & Oncology, Nagoya City University Graduate School of Medical Sciences

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1: IDO)はトリプトファン(Trp)をキヌレニン(Kyn)に異化する経路の酵素で,抗腫瘍免疫応答を抑制する腫瘍微小環境内の重要な因子の一つである。本研究では成人T細胞性白血病/リンパ腫(ATL)においてATL細胞および腫瘍微小環境中の細胞がIDOを産生し,腫瘍微小環境のみならず血液中においてもKyn/Trp比およびKyn濃度の上昇をもたらし,血清Kyn/Trp比およびKyn濃度高値はATLにおける独立した予後不良因子であることを明らかにした。このように血清中のKynおよびTrp濃度の測定は,個々のATL患者の予後を予測するために有用である。さらにIDOは現在,さまざまながん種においてがん免疫療法の有望な標的と考えられている。本研究はATLにおいてもIDOが新規がん免疫療法の標的分子として有望であることを示すものである。

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

Codes

  • NII Article ID (NAID)
    130005130183
  • NII NACSIS-CAT ID (NCID)
    AN00252940
  • Text Lang
    JPN
  • ISSN
    0485-1439
  • NDL Article ID
    026962484
  • NDL Call No.
    Z19-295
  • Data Source
    NDL  J-STAGE 
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