Clinical significance of tryptophan catabolism in Hodgkin lymphoma. Issue 1 (29th November 2017)

• Record Type: Journal Article
• Authors: Masaki, Ayako; Ishida, Takashi; Maeda, Yasuhiro; Ito, Asahi; Suzuki, Susumu; Narita, Tomoko; Kinoshita, Shiori; Takino, Hisashi; Yoshida, Takashi; Ri, Masaki; Kusumoto, Shigeru; Komatsu, Hirokazu; Inagaki, Hiroshi; Ueda, Ryuzo; Choi, Ilseung; Suehiro, Youko; Iida, Shinsuke
• Is Part Of: Cancer science. Volume 109:Issue 1(2018)
• Page Start: 74
• Page End: 83
• Publication Date: 2017-11-29
• Subjects: Hodgkin lymphoma -- indoleamine 2, 3‐dioxygenase -- innate immunity -- kynurenine -- tryptophan; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13432
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : 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, 15‐81 years; median, 45 years), 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 5 years, 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 <285.6 ng/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. Abstract : A high serum Kyn/Trp ratio was a significant detrimental prognostic factor in Hodgkin Lymphoma. Measurement of serum Kyn and Trp concentrations will be useful for predicting prognosis of the individual Hodgkin Lymphoma patient. Hodgkin Lymphoma, especially in patients with a high serum Kyn/Trp ratio, is an appropriate disease for testing these novel cancer immunotherapies targeting IDO.