Significantly different immunological score in lung adenocarcinoma and squamous cell carcinoma and a proposal for a new immune staging system

TNM stage is not enough to accurately predict the prognosis of patients with non-small cell lung cancer (NSCLC). This study aimed to establish the immunological score (IS) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), separately, and propose a new staging system in NSCLC. We used the multiplex fluorescent immunohistochemistry (mIHC) technology to detect 17 immune biomarkers of 304 patients with NSCLC. The LASSO-COX regression model was used to establish the IS(NSCLC) in the training cohorts. The IS(NSCLC) was then validated in the validation cohort. The constructed IS(LUAD) contained three immune features: CD4(+)CD73(+)(core of tumor (CT)), PD-L1(+)(CT), and IDO(+)(invasive margin (IM)). IS(LUSC) also contained two immune features: CD8(+)CD39(−)CD73(−)(CT), CD8(+)Tim-3(+)(IM). In the training cohort, significant prognostic differences were found upon comparing low-IS(NSCLC) patients with high-IS(NSCLC) patients. For LUAD, the 5-y disease-free survival (DFS) rates were 54.7% vs. 8.1% and the 5-y overall survival (OS) rates were 82.4% vs. 36% (all P< .0001). For LUSC, the 5-y DFS rates were 74.0% vs. 14.7% and the 5-y OS rates were 78.2% vs. 17.6% (all P< .0001). Multivariate analyses indicated that IS(NSCLC) was an independent indicator for prognosis. Finally, we combined IS(NSCLC) with clinicopathological factors to establish a TN-I staging system and two nomogram models for clinical use. The TN-I stage had better prediction accuracy than TNM stage. The newly established IS(LUAD) and IS(LUSC) were completely different, and both were excellent indicators for the prognostic prediction. The TN-I stage could effectively improve prognostic accuracy and facilitate clinical application. Abbreviations NSCLC, non-small cell lung cancer; IS, immunological score; mIHC, multiplex fluorescent immunohistochemistry; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; CT, core of tumor; IM, invasive margin; DFS, disease-free survival; OS, overall survival; SITC, the Society for Immunotherapy of Cancer; FFPE, formalin-fixed paraffin-embedded; MWT, microwave treatment; DCA, decision curve analysis; ROC, receiver operating characteristic; AUC, area under the curve; EGFR, epidermal growth factor receptor.