Prognostic Significance of Tryptophan Catabolism in Adult T-cell Leukemia/Lymphoma

被引:40
作者
Masaki, Ayako [1 ,2 ]
Ishida, Takashi [1 ]
Maeda, Yasuhiro [3 ]
Suzuki, Susumu [4 ]
Ito, Asahi [1 ]
Takino, Hisashi [2 ]
Ogura, Hiroka [1 ]
Totani, Haruhito [1 ]
Yoshida, Takashi [1 ]
Kinoshita, Shiori [1 ]
Narita, Tomoko [1 ]
Ri, Masaki [1 ]
Kusumoto, Shigeru [1 ]
Inagaki, Atsushi [5 ]
Komatsu, Hirokazu [1 ]
Niimi, Akio [6 ]
Ueda, Ryuzo [4 ]
Utsunomiya, Atae [7 ]
Inagaki, Hiroshi [2 ]
Iida, Shinsuke [1 ]
机构
[1] Nagoya City Univ, Grad Sch Med, Dept Hematol & Oncol, Nagoya, Aichi 4678601, Japan
[2] Nagoya City Univ, Grad Sch Med Sci, Dept Anat Pathol & Mol Diagnost, Nagoya, Aichi 4678601, Japan
[3] Nagoya City Univ, Grad Sch Pharmaceut Sci, Lab Hosp Pharm, Nagoya, Aichi 4678601, Japan
[4] Aichi Med Univ, Sch Med, Dept Tumor Immunol, Aichi, Japan
[5] Nagoya City West Med Ctr, Dept Hematol & Oncol, Aichi, Japan
[6] Nagoya City Univ, Grad Sch Med Sci, Dept Resp Med Allergy & Rheumatol, Nagoya, Aichi 4678601, Japan
[7] Imamura Bun In Hosp, Dept Hematol, Kagoshima, Japan
关键词
INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION; MONOCLONAL-ANTIBODY KW-0761; LEUKEMIA-LYMPHOMA; CLINICAL-SIGNIFICANCE; INHIBITION; CANCER; SERUM; TAX; PROLIFERATION; THERAPY;
D O I
10.1158/1078-0432.CCR-14-2275
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO), an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, is increasingly being recognized as an important micro-environmental 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). 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 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. (C)2015 AACR.
引用
收藏
页码:2830 / 2839
页数:10
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