Abstract

Background: Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme that converts tryptophan (Trp) to kynurenine (Kyn), suppresses antitumor immune responses via depletion of Trp and accumulation of Kyn. We hypothesized that, in colorectal cancer (CRC), IDO activity may serve as a biomarker and thus we compared the IDO activity between patients with CRC and those without CRC. We further assessed the effect of surgical treatment of CRC on IDO activity.Methods: Serum concentrations of Trp and Kyn were measured by high performance liquid chromatography in the sera of 68 patients with CRC (CRC group) and 38 without CRC (Control group) prior surgery (D0) and 7 days after surgery (D7). The IDO activity was estimated by the serum Kyn-to-Trp ratio (Kyn/Trp ratio).Results: At Day 0, serum Kyn concentration was higher in the CRC group than in Control group (1.7 [1.4;2.1] μM vs 1.25 [0.9;1.78] μM, respectively; p=0.004) while no difference in serum concentration of Trp was observed between the two groups. Kyn/Trp ratio (IDO activity) was significantly higher in the CRC group than in Control group. At Day 7 serum concentrations of Trp, Kyn and the Kyn/Trp ratio were not statistically different between the two groups.Conclusion: This study indicates that IDO activity is higher in patients with CRC compared with those without CRC. Surgical treatment impacts the IDO activity with a similar Kyn/Trp ratio in both groups. This study is the first step to larger studies to establish the Kyn/Trp ratio as a reliable serum marker of CRC.

Highlights

  • Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme that catalyzes the conversion of tryptophan (Trp) to kynurénine (Kyn) [1]

  • These conflicting results suggest that more data are needed on IDO activity in colorectal cancer to determine whether activation of tryptophan catabolism by IDO may serve as a biomarker of CRC

  • The results of this study indicate that IDO activity assessed by serum Kyn/Trp ratio is higher in patients with CRC compared with those without CRC before the surgical removal of the CCR

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Summary

Introduction

Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme that catalyzes the conversion of tryptophan (Trp) to kynurénine (Kyn) [1]. Increased IDO activity have been reported in several types of cancers such as skin [4] breast [5] and lung cancer [6] and have even been associated with disease progression and poor prognosis in lung [6] and skin cancer [4]. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme that converts tryptophan (Trp) to kynurenine (Kyn), suppresses antitumor immune responses via depletion of Trp and accumulation of Kyn. We hypothesized that, in colorectal cancer (CRC), IDO activity may serve as a biomarker and we compared the IDO activity between patients with CRC and those without CRC. We further assessed the effect of surgical treatment of CRC on IDO activity

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