The association between indoleamine 2, 3-dioxygenase activity and clinical prognosis in patients with early stage non-small cell lung cancer after stereotactic radiotherapy

Objective: To explore the changes in activity of indoleamine 2, 3-dioxygenase (IDO) before and after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC) and its relationship with survival. Methods: The retrospective study was to assess IDO activity by serum kynurenine (Kyn) and Kyn to tryptophan (Trp) ratio before and after SBRT of early stage NSCLC. Thirty early stage NSCLC patients who received SBRT in the Cancer Hospital of the University of Chinese Academy of Sciences were enrolled, from December 2014 to July 2017. High-performance liquid chromatography and mass spectrometry were used to detect serum Kyn and Trp before and after SBRT. The ratios of Kyn after SBRT to Kyn before SBRT were divided into high and low group according to the median value. Similarly, the ratios of Kyn to Trp after SBRT were divided into high and low group. The correlation between overall survival (OS), progression-free survival (PFS) and IDO activity was evaluated. The factors influencing prognosis were analyzed. Results: In all patients, lower ratio of Kyn after SBRT to Kyn before SBRT significantly was correlated with better PFS (median PFS: not reached;vs. 26.8 months, HR = 0.31, 95% CI = 0.11-0.90, P < 0.05). The lower Kyn: Trp ratio after SBRT had longer OS (median OS: not reached vs. 36.5 months, HR = 0.27, 95% CI = 0.079-0.95, P < 0.05). In multivariate analysis, smoking < 30 packs/year, higher BED, and lower ratio of Kyn after SBRT to Kyn before SBRT were associated with longer PFS. Lower Kyn: Trp ratio after SBRT and higher BED were associated with longer OS. Conclusions: SBRT could alter IDO-mediated antitumor immune activity. IDO is a potentially valuable biomarker for monitoring immune status and predicting survival in early NSCLC patients after SBRT. (authors)