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

Abstract

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.

Keywords: Non-small cell lung cancer; immunological score; lung adenocarcinoma; lung squamous cell carcinoma; prognosis; staging.