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Lookup NU author(s): Dr Lei HuangORCiD, Emeritus Professor Andrew MellorORCiD
Host 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 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.
Author(s): Wang W, Huang L, Jin JY, Jolly S, Zang Y, Wu H, Yan L, Pi W, Li L, Mellor AL, Kong FS
Publication type: Article
Publication status: Published
Journal: Cancer Research
Year: 2018
Volume: 78
Issue: 3
Pages: 809-816
Print publication date: 01/02/2018
Online publication date: 08/11/2017
Acceptance date: 24/10/2017
Date deposited: 15/11/2017
ISSN (print): 0008-5472
ISSN (electronic): 1538-7445
Publisher: American Association for Cancer Research
URL: https://doi.org/10.1158/0008-5472.CAN-17-2995
DOI: 10.1158/0008-5472.CAN-17-2995
PubMed id: 29118088
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