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

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 exp...

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Main Authors:	Eun Hee Jung, Hee Ryeong Jang, Se Hyun Kim, Koung Jin Suh, Yu Jung Kim, Ju‐Hyun Lee, Jin‐Haeng Chung, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong‐Wan Kim, Dae Seog Heo, Jong Seok Lee
Format:	Article
Language:	English
Published:	Wiley 2021-03-01
Series:	Thoracic Cancer
Subjects:	immune checkpoint inhibitor LAG‐3 non‐small cell lung cancer NY‐ESO‐1 PD‐L1
Online Access:	https://doi.org/10.1111/1759-7714.13834

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collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Eun Hee Jung Hee Ryeong Jang Se Hyun Kim Koung Jin Suh Yu Jung Kim Ju‐Hyun Lee Jin‐Haeng Chung Miso Kim Bhumsuk Keam Tae Min Kim Dong‐Wan Kim Dae Seog Heo Jong Seok Lee
spellingShingle	Eun Hee Jung Hee Ryeong Jang Se Hyun Kim Koung Jin Suh Yu Jung Kim Ju‐Hyun Lee Jin‐Haeng Chung Miso Kim Bhumsuk Keam Tae Min Kim Dong‐Wan Kim Dae Seog Heo Jong Seok Lee Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer Thoracic Cancer immune checkpoint inhibitor LAG‐3 non‐small cell lung cancer NY‐ESO‐1 PD‐L1
author_facet	Eun Hee Jung Hee Ryeong Jang Se Hyun Kim Koung Jin Suh Yu Jung Kim Ju‐Hyun Lee Jin‐Haeng Chung Miso Kim Bhumsuk Keam Tae Min Kim Dong‐Wan Kim Dae Seog Heo Jong Seok Lee
author_sort	Eun Hee Jung
title	Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer
title_short	Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer
title_full	Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer
title_fullStr	Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer
title_full_unstemmed	Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer
title_sort	tumor lag‐3 and ny‐eso‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer
publisher	Wiley
series	Thoracic Cancer
issn	1759-7706 1759-7714
publishDate	2021-03-01
description	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.
topic	immune checkpoint inhibitor LAG‐3 non‐small cell lung cancer NY‐ESO‐1 PD‐L1
url	https://doi.org/10.1111/1759-7714.13834
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spelling	doaj-9a59e24b81d14ef68c483b16c731fa9c2021-03-01T11:33:19ZengWileyThoracic Cancer1759-77061759-77142021-03-0112561963010.1111/1759-7714.13834Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancerEun Hee Jung0Hee Ryeong Jang1Se Hyun Kim2Koung Jin Suh3Yu Jung Kim4Ju‐Hyun Lee5Jin‐Haeng Chung6Miso Kim7Bhumsuk Keam8Tae Min Kim9Dong‐Wan Kim10Dae Seog Heo11Jong Seok Lee12Department of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaDepartment of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaDepartment of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaDepartment of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaDepartment of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaDepartment of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaDepartment of Pathology, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaDepartment of Internal Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartment of Internal Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartment of Internal Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartment of Internal Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartment of Internal Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartment of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam South KoreaAbstract 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.https://doi.org/10.1111/1759-7714.13834immune checkpoint inhibitorLAG‐3non‐small cell lung cancerNY‐ESO‐1PD‐L1

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

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