Jornal de Imunologia Clínica e Celular
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Measurement of Indoleamine 2, 3 Dioxygenase Activity in Colorectal Cancer: A Controlled Group Study

Daniel Eyraud, Benjamin Granger, Noel Zahr, Frédéric Charlotte, Armelle Bardier, Gaëlle Gottrand, Audrey Perez-Lascar, Mehdi Karoui, Louis Lemoine, Jean Christophe Vaillant, David Klatzmann, Laurent Hannoun and Pierre Coriat

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.