title: Prognostic Significance of Tryptophan Catabolism in Adult T-cell Leukemia/Lymphoma.
abstract: OBJECTIVE
  Indoleamine 2,3-dioxygenase 1 (IDO1: IDO), an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, is increasingly being recognized as an important microenvironmental factor suppressing antitumor immune responses. The purpose of the present study was to determine the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL).
  
  
  METHODS
  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 volunteer controls. The relationships between various clinical parameters including overall survival 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 healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. However, there were no significant differences in the serum Trp concentrations between ATL patients, HTLV-1 ACs, and controls. IDO was possibly produced by ATL and/or cells of the microenvironment. Multivariate analyses demonstrated that a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, were significantly independent detrimental prognostic factors in ATL, as well as in that subset of patients with aggressive variant ATL.
  
  
  CONCLUSIONS
  Quantification of serum Kyn and Trp is useful for predicting prognosis of an individual ATL patient. Furthermore, ATL, especially in patients with a high serum Kyn/Trp ratio, is an appropriate disease for testing novel cancer immunotherapies targeting IDO.
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan. Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Ayako
authors: A
authors: Masaki
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan. itakashi@med.nagoya-cu.ac.jp.
authors: Takashi
authors: T
authors: Ishida
authors: Laboratory of Hospital Pharmacy, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Aichi, Japan.
authors: Yasuhiro
authors: Y
authors: Maeda
authors: Department of Tumor Immunology, Aichi Medical University School of Medicine, Aichi, Japan.
authors: Susumu
authors: S
authors: Suzuki
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Asahi
authors: A
authors: Ito
authors: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Hisashi
authors: H
authors: Takino
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Hiroka
authors: H
authors: Ogura
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Haruhito
authors: H
authors: Totani
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Takashi
authors: T
authors: Yoshida
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Shiori
authors: S
authors: Kinoshita
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Tomoko
authors: T
authors: Narita
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Masaki
authors: M
authors: Ri
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Shigeru
authors: S
authors: Kusumoto
authors: Department of Hematology and Oncology, Nagoya City West Medical Center, Nagoya, Aichi, Japan.
authors: Atsushi
authors: A
authors: Inagaki
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Hirokazu
authors: H
authors: Komatsu
authors: Department of Respiratory Medicine, Allergy and Rheumatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Akio
authors: A
authors: Niimi
authors: Department of Tumor Immunology, Aichi Medical University School of Medicine, Aichi, Japan.
authors: Ryuzo
authors: R
authors: Ueda
authors: Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan.
authors: Atae
authors: A
authors: Utsunomiya
authors: Department of Anatomic Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Hiroshi
authors: H
authors: Inagaki
authors: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Shinsuke
authors: S
authors: Iida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007737:Kynurenine / Q000097:blood / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007737:Kynurenine; D014364:Tryptophan