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

Abstract

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.

• Authors: Ayako Masaki, Takashi Ishida, Yasuhiro Maeda, Susumu Suzuki, Asahi Ito, Hisashi Takino, Haruhito Totani, Takashi Yoshida, Shiori Kinoshita, Hiroka Ogura, Tomoko Narita, Masaki Ri, Shigeru Kusumoto, Atsushi Inagaki, Hirokazu Komatsu, Akio Niimi, Ryuzo Ueda, Atae Utsunomiya, Hiroshi Inagaki, Shinsuke Iida
• Journal: [Rinsho ketsueki] The Japanese journal of clinical hematology (Rinsho Ketsueki) Vol. 56 Issue 11 Pg. 2295-304 (Nov 2015) ISSN: 0485-1439 [Print] Japan
• PMID: 26666715 (Publication Type: English Abstract, Journal Article)

Chemical References

• Tryptophan

Topics

• Aged
• Female
• HTLV-I Infections (complications)
• Humans
• Leukemia-Lymphoma, Adult T-Cell (diagnosis, metabolism, virology)
• Male
• Multivariate Analysis
• Prognosis
• Tryptophan (metabolism)