Clinical significance of tryptophan catabolism in follicular lymphoma

Ayako Masaki, Takashi Ishida, Yasuhiro Maeda, Asahi Ito, Susumu Suzuki, Tomoko Narita, Shiori Kinoshita, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Hiroshi Inagaki, Ryuzo Ueda, Ilseung Choi, Youko Suehiro, Shinsuke Iida

Research output: Contribution to journalArticlepeer-review

Abstract

The enzyme, indoleamine 2,3-dioxygenase 1 (IDO), catabolizes tryptophan (Trp) in the kynurenine (Kyn) pathway, and is important in suppressing antitumor immune responses in the tumor microenvironment. With regard to previously untreated patients with follicular lymphoma (FL), we sought to establish the prognostic significance of Trp catabolism in this disease. Serum Trp and Kyn levels in 110 patients with FL were quantified, and their relationship to different clinical parameters studied. IDO expression in the lymph nodes of affected patients was studied. Study participants included 54 males and 56 females (age range 39–86, median 62 years), showing a 5-year overall survival (OS) rate of 78.5%. Patients with a high Kyn level (5-year OS, 65.0% vs. 81.7%; p = 0.026), high Kyn/Trp ratio (71.1% vs. 81.7%; p = 0.002), and low hemoglobin (Hb) level (<12.0 g/dL; p = 0.001; a component of FL international prognostic indexes) demonstrated a significantly shorter OS. Multivariate analysis included the following 10 variables: age, sex, serum β2-microglobulin, Hb, longest diameter of the largest involved node, Ann Arbor stage, serum lactate dehydrogenase, histologic grading, B symptoms, and serum Kyn/Trp ratio; a lower Hb level and a high Kyn/Trp ratio (HR, 3.239; 95% CI, 1.296–8.096) led to a significantly inferior OS. In the microenvironment, some CD11c-positive myeloid dendritic cells but not FL tumor cells were found to produce IDO. Overall, measuring levels of serum Kyn and Trp in individual patients with FL contributed to predicting their prognosis.

Original languageEnglish
Pages (from-to)742-753
Number of pages12
JournalHematological Oncology
Volume38
Issue number5
DOIs
Publication statusPublished - 12-2020

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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