Wang, WeiliHuang, LeiJin, Jian-YueJolly, ShrutiZang, YongWu, HuanmeiYan, LiPi, WenhuLi, LangMellor, Andrew L.Kong, Feng-Ming Spring2019-07-302019-07-302018-02-01Wang, W., Huang, L., Jin, J. Y., Jolly, S., Zang, Y., Wu, H., … Kong, F. S. (2018). IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients. Cancer research, 78(3), 809–816. doi:10.1158/0008-5472.CAN-17-2995https://hdl.handle.net/1805/20043Host immunity influences the impact of radiotherapy (RT) in cancer, but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non-small cell lung cancer (NSCLC). IDO-mediated production of kynurenine and the kynurenine:tryptophan ratio in patient blood serum were determined for stage III NSCLC patients at times before, during, and after RT administration and then correlated to overall survival (OS), progression-free survival, and disease progression rate in patients. We found the impact of RT on these serum IDO markers to be heterogeneous in patients. On average, kynurenine:tryptophan ratios were reduced during RT but restored after RT. Notably, both baseline levels of kynurenine:tryptophan and changes in the levels of kynurenine after RT were significantly associated with OS. When combined, favorable change and favorable baseline corresponded with very long-term OS (median OS was not reached after 57 months of median follow-up). Favorable change combined with unfavorable baseline still corresponded with a lack of distant metastases. Our results suggest that RT alters IDO-mediated immune status in NSCLC patients and that changes in this serum biomarker may be useful to predict outcomes and perhaps personalize RT dosage to improve survival.Significance: Radiotherapy appears to influence systemic IDO activity and to exert a significant impact on metastatic risk and overall survival, with possible implications for defining a biomarker to optimize radiation dose in patients to improve outcomes. Cancer Res; 78(3); 809-16. ©2017 AACR.en-USPublisher PolicyAdenocarcinomaCarcinoma -- Non-Small-Cell LungCarcinoma -- Squamous CellIndoleamine-Pyrrole 2,3,-DioxygenaseLung NeoplasmsArticle