Clinical significance of tryptophan catabolism in Hodgkin lymphoma

被引：25

作者：

Masaki, Ayako ^{[1
,2
]}

Ishida, Takashi ^{[1
]}

Maeda, Yasuhiro ^{[3
]}

Ito, Asahi ^{[1
]}

Suzuki, Susumu ^{[4
]}

Narita, Tomoko ^{[1
]}

Kinoshita, Shiori ^{[1
]}

Takino, Hisashi ^{[2
]}

Yoshida, Takashi ^{[1
]}

Ri, Masaki ^{[1
]}

Kusumoto, Shigeru ^{[1
]}

Komatsu, Hirokazu ^{[1
]}

Inagaki, Hiroshi ^{[2
]}

Ueda, Ryuzo ^{[4
]}

Choi, Ilseung ^{[5
]}

Suehiro, Youko ^{[5
]}

Iida, Shinsuke ^{[1
]}

机构：

[1] Nagoya City Univ, Dept Hematol & Oncol, Grad Sch Med Sci, Nagoya, Aichi, Japan

[2] Nagoya City Univ, Dept Anat Pathol & Mol Diagnost, Grad Sch Med Sci, Nagoya, Aichi, Japan

[3] Nagoya City Univ, Lab Hosp Pharm, Grad Sch Pharmaceut Sci, Nagoya, Aichi, Japan

[4] Aichi Med Univ, Dept Tumor Immunol, Sch Med, Nagakute, Aichi, Japan

[5] Natl Kyushu Canc Ctr, Dept Hematol, Fukuoka, Japan

来源：

CANCER SCIENCE | 2018年 / 109卷 / 01期

关键词：

Hodgkin lymphoma; indoleamine; 2; 3-dioxygenase; innate immunity; kynurenine; tryptophan; TUMOR-ASSOCIATED MACROPHAGES; INDOLEAMINE 2,3-DIOXYGENASE; SOLUBLE CD30; PROGNOSTIC-SIGNIFICANCE; SERUM-LEVELS; T-CELLS; DISEASE; CANCER; EXPRESSION; IDO;

D O I：

10.1111/cas.13432

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly diagnosed Hodgkin lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 concentration. The IDO expression was evaluated in the patients' affected lymph nodes. The cohort comprised 22 male and 30 female patients (age range, 15-81years; median, 45years), with a 5-year overall survival (OS) of 88.6%. The OS was significantly shorter for patients with a high Kyn/Trp ratio (OS at 5years, 60.0% vs 92.2%), for those with stage IV disease, and for those with lymphocytopenia (<600/mm(3) and/or <8% white blood cell count). The latter two parameters are components of the international prognostic score for advanced HL. In contrast, there were no significant differences in OS according to age, serum albumin, hemoglobin, sex, white blood cell count, or serum soluble CD30 ( or <285.6ng/mL). Multivariate analysis using the three variables stage, lymphocytopenia, and serum Kyn/Trp ratio showed that only the latter significantly affected OS. Indoleamine 2,3-dioxygenase 1 was produced by macrophages/dendritic cells, but not by HL tumor cells, and IDO levels determined by immunohistochemistry had a significant positive correlation with the serum Kyn/Trp ratio. In conclusion, quantification of serum Kyn and Trp is useful for predicting prognosis of individual HL patients.

引用

页码：74 / 83

页数：10