Abstract
The role of distinct immune cell types in modulating cancer progression has recently gained attention. The immune context is indicated by the abundance of immune infiltration based on quantified lymphocytes in the core of tumors (CT) and invasive tumor margin (IM). Novel immune biomarkers could potentially complement tumor-node-metastasis (TNM) classification for non-small cell lung cancers (NSCLCs), thereby improving prognostic accuracy. This study evaluated the prognostic value of a newly established immunologic score (neo-IS) in patients with NSCLC. We detected 10 immune biomarkers, including CD45RO, CD3, CD8, CD68, CD163, CD66b, FoxP3, PD-1, PD-L1, and TIM-3, in 350 patients with NSCLC from 2 cohorts using immunohistochemistry (IHC). The 3- and 5-year survival and overall survival (OS) rates were evaluated. An immunologic prediction model specifically for NSCLC patients, the neo-immunologic score (neo-ISNSCLC ), was constructed using a Cox proportional hazards regression model. In the discovery cohort (n = 250), the establishment of neo-ISNSCLC was based on 4 immune biomarkers: CD3+IM , CD8+CT , FoxP3+IM , and PD-1+IM . Significant prognostic differences were found upon comparing low-ISNSCLC patients and high-ISNSCLC patients. The OS rate in the high-ISNSCLC group was significantly longer than that in the low-ISNSCLC group (67.5 months vs. 51.2 months, p < 0.001). The neo-ISNSCLC was validated in the validation cohort (n = 100), and the results were confirmed. Multivariate analyses indicated that neo-ISNSCLC was an independent indicator of prognosis in patients with NSCLC. Finally, we combined neo-ISNSCLC with clinicopathologic factors to establish a tumor-node-metastasis-immune (TNM-I) staging system for clinical use, which showed better prediction accuracy than the TNM stage.