ImmuneScore as a novel RNA-based prognostic signature superior to PD-L1 in advanced non-squamous NSCLC patients receiving chemotherapy combined with immune checkpoint inhibitor therapy

Abstract

Aim: Our study aimed to explore the prognostic predictive potential of a novel RNA-based signature called ImmuneScore in advanced non-squamous NSCLC patients receiving combined immune checkpoint inhibitor (ICI) treatment and chemotherapy. Methods: RNA-sequencing data of 113 patients screened out from ORIENT-11 trial were retrospectively analyzed. ImmuneScore was calculated by the ESTIMATE algorithm. The association of ImmuneScore with early tumor progression, progression-free survival (PFS), and overall survival (OS) was analyzed using chi-square test, Cox regression test, and log-rank test. Receiver operating characteristic (ROC) curves were generated, with higher values of area under the ROC curves (AUCs) indicating better prediction ability. Results: ImmuneScore was negatively correlated with early tumor progression rate (4.3% vs. 18.6%, P = 0.013) while positively correlated with PFS (HR = 0.29, 95%CI: 0.16-0.53, P < 0.001) and OS (HR = 0.32,95%CI: 0.18-0.58, P < 0.001), demonstrating higher AUCs than that of Programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) (early tumor progression: 0.64 vs. 0.68; PFS: 0.67 vs. 0.58; OS: 0.73 vs. 0.63). Nomograms integrating ImmuneScore and other significant variables (age and T-stage for PFS, gender and T-stage for OS) yielded good performance in PFS and OS prediction. Conclusion: ImmuneScore serves as a novel RNA-based prognostic signature superior to PD-L1 in advanced non-squamous NSCLC patients receiving chemotherapy combined with ICI therapy. Higher ImmuneScore indicates lower early tumor progression rate, longer PFS, and longer OS.