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Tumor LAG-3 and NY-ESO-1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer

Cited 7 time in Web of Science Cited 8 time in Scopus
Authors

Jung, Eun Hee; Jang, Hee Ryeong; Kim, Se Hyun; Suh, Koung Jin; Kim, Yu Jung; Lee, Ju-Hyun; Chung, Jin-Haeng; Kim, Miso; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong-Wan; Heo, Dae Seog; Lee, Jong Seok

Issue Date
2021-03
Publisher
Blackwell Publishing Asia Pty Ltd
Citation
Thoracic Cancer, Vol.12 No.5, pp.619-630
Abstract
Background: Immune checkpoint inhibitors (ICIs) are an established treatment for non-small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested NY-ESO-1 and LAG-3 to be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of their expression in NSCLC. Methods: We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti-PD-1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum-based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY-ESO-1, LAG-3, and PD-L1 expression, whose ability to predict progression-free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values. Results: NY-ESO-1 or LAG-3 expression was detected in all tumor samples from patients with high PD-L1 expression and was significantly associated with favorable outcomes, unlike PD-L1 expression. Patients with both NY-ESO-1- and LAG-3-expressing tumors had a high DCB rate and those with triple-positive PD-L1, LAG-3, and NY-ESO expression had a superior median OS and PFS than those with triple-negative expression. Furthermore, LAG-3 and NY-ESO-1 co-expression was an independent predictor of both PFS and OS, while LAG-3 displayed a good NPV. Conclusions: Patients with NSCLC who co-express NY-ESO-1 or LAG-3 with PD-L1 exhibit greater DCBs and improved long-term survival following anti-PD-1 therapy. Moreover, NY-ESO-1 and LAG-3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.
ISSN
1759-7706
URI
https://hdl.handle.net/10371/179104
DOI
https://doi.org/10.1111/1759-7714.13834
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