TY - JOUR
T1 - Prognostic significance of Tryptophan catabolism in adult t-cell leukemia/lymphoma
AU - Masaki, Ayako
AU - Ishida, Takashi
AU - Maeda, Yasuhiro
AU - Suzuki, Susumu
AU - Ito, Asahi
AU - Takino, Hisashi
AU - Ogura, Hiroka
AU - Totani, Haruhito
AU - Yoshida, Takashi
AU - Kinoshita, Shiori
AU - Narita, Tomoko
AU - Ri, Masaki
AU - Kusumoto, Shigeru
AU - Inagaki, Atsushi
AU - Komatsu, Hirokazu
AU - Niimi, Akio
AU - Ueda, Ryuzo
AU - Utsunomiya, Atae
AU - Inagaki, Hiroshi
AU - Iida, Shinsuke
N1 - Publisher Copyright:
© 2015 AACR.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/6/15
Y1 - 2015/6/15
N2 - 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 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). 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.
AB - 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 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). 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.
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U2 - 10.1158/1078-0432.CCR-14-2275
DO - 10.1158/1078-0432.CCR-14-2275
M3 - Article
C2 - 25788494
AN - SCOPUS:84941953178
VL - 21
SP - 2830
EP - 2839
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 12
ER -