Association between IDO activity and prognosis in patients with non-small cell lung cancer after radiotherapy.

Content Provider	Europe PMC
Author	Zhu, Yaoyao Jiang, Chenxue Liu, Yuanjun Li, Yefei Wu, He Feng, Jianguo Xu, Yaping
Copyright Year	2020
Abstract	BackgroundIndoleamine 2,3-dioxygenase (IDO), a limiting enzyme in the IDO/kynurenine (Kyn) pathway, converts tryptophan (Trp) into Kyn, and plays a significant role in immune suppression and tumor immune evasion. This study aimed to investigate the association between IDO activity and clinical outcomes in non-small cell lung cancer (NSCLC) patients who underwent radiotherapy (RT).MethodsSerum Kyn and Trp levels were measured in 104 NSCLC patients by high-performance liquid chromatography at baseline, and the following RT. The correlation between IDO activity, as computed by Kyn: Trp ratios and survival was estimated using Kaplan-Meier curves. Cox proportional hazard models are used in the univariate and multivariate analyses.ResultsBoth the Kyn levels and Kyn:Trp ratios were reduced after RT at a biologically equivalent dose (BED) of <70 Gy, while these increased at a BED of ≥70 Gy. Post/pre-Kyn levels were positively correlated with an objective response. Patients with a higher Kyn:Trp ratio pre-RT had the worse median progression-free survival (mPFS, 13.5 vs. 24.5 months, P=0.049). Higher post/pre-Kyn:Trp ratios were correlated with improved median overall survival (mOS, 23.8 months vs. not reached, P=0.032). On the multivariate analysis, pre-RT Kyn:Trp and post/pre-Kyn:Trp ratios remained as independent predictive factors for PFS and OS, respectively.ConclusionsIt was proved that RT could alter IDO-mediated immune activity and establish strong correlations between IDO activity and survival outcomes in NSCLC patients treated with RT. These present findings suggest that the profiling of IDO activity might allow for the prompt adjustment of RT doses and better predict patient response to RT.
ISSN	23055839
Volume Number	8
PubMed Central reference number	PMC7576049
Issue Number	18
PubMed reference number	33241018
Journal	Annals of Translational Medicine [Ann Transl Med]
e-ISSN	23055847
DOI	10.21037/atm-20-5634
Language	English
Publisher	AME Publishing Company
Publisher Date	2020-09-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2020 Annals of Translational Medicine. All rights reserved.
Subject Keyword	Indoleamine 2,3-dioxygenase activity (IDO activity) radiotherapy-induced immune response non-small cell lung cancer (NSCLC) prognosis
Content Type	Text
Resource Type	Article
Subject	Medicine