Abstract
BackgroundImmune 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.MethodsWe 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.ResultsNY‐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.ConclusionsPatients 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.
Highlights
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 that NY-ESO-1 and Lymphocyte activation gene-3 (LAG-3) could be surrogate markers of ICI responses in NSCLC; we explored the predictive value of NY-ESO-1 and LAG-3 expression in NSCLC
The Checkmate-227 clinical trial revealed that patients with chemo-naïve NSCLC with PD-L1 expression (TPS > 1%) who received dual checkpoint blockade with nivolumab and ipilimumab displayed greater survival benefits than those who received platinum-based chemotherapy [2]
Summary
Since both tumor-infiltrated T cells and the cancer-specific antigens that they recognize are crucial for generating effective anti-cancer immune reactions after ICI administration, we aimed to assess the predictive value of NY-ESO-1 and LAG-3 for ICIs and to identify patients with advanced NSCLC who may receive clinical benefits from PD-1 antibody treatment
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