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. 2020 Sep;8(18):1169.
doi: 10.21037/atm-20-5634.

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

Yaoyao Zhu  1   2 , Chenxue Jiang  1 , Yuanjun Liu  1   2 , Yefei Li  1 , He Wu  2 , Jianguo Feng  3 , Yaping Xu  1   2
Affiliations

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

Yaoyao Zhu et al. Ann Transl Med. 2020 Sep.

Abstract

Background: Indoleamine 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).

Methods: Serum 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.

Results: Both 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.

Conclusions: It 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.

Keywords: Indoleamine 2,3-dioxygenase activity (IDO activity); non-small cell lung cancer (NSCLC); prognosis; radiotherapy-induced immune response.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5634). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Dynamic changes of IDO-associated molecular activity. (A) The plot reveals the individual and mean activity levels for kynurenine. (B) The Kyn:Trp ratio at pre-RT and post-RT under different BED. Bars: median, standard deviation. The P values were calculated using the unpaired Student’s t-tests. IDO, indoleamine 2,3-dioxygenase; Trp, tryptophan; Kyn, kynurenine; RT, radiotherapy; BED, biologically equivalent doses.
Figure 2
Figure 2
Baseline IDO-mediated immune activity and treatment outcomes. (A) The pre-RT Kyn:Trp ratio for progression-free survival. (B) The pre-RT Kyn:Trp ratio for overall survival. IDO, indoleamine 2,3-dioxygenase; RT, radiotherapy; Trp, tryptophan; Kyn, kynurenine; CI, confidence interval.
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