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

Yaoyao Zhu; Chenxue Jiang; Yuanjun Liu; Yefei Li; He Wu; Jianguo Feng; Yaping Xu

doi:10.21037/atm-20-5634

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

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

Authors

Yaoyao Zhu^{1

2}, Chenxue Jiang¹, Yuanjun Liu^{1

2}, Yefei Li¹, He Wu², Jianguo Feng³, Yaping Xu^{1

2}

Affiliations

¹ Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
² First Clinical Medical School, Wenzhou Medical University, Wenzhou, China.
³ Laboratory Research Centre, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

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.