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

来源：

CLINICAL CANCER RESEARCH | 2015年 / 21卷 / 12期

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

页码：2830 / 2839

页数：10

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[1] The targeting of immunosuppressive mechanisms in hematological malignancies [J].