Significantly different immunological score in lung adenocarcinoma and squamous cell carcinoma and a proposal for a new immune staging system
Ziqing Zeng, Fan Yang, Yunliang Wang, Hua Zhao, Feng Wei, Peng Zhang, Xiying Zhang, Xiubao Ren
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 ISNSCLC in the training cohorts. The ISNSCLC was then validated in the validation cohort. The constructed ISLUAD contained three immune features: CD4+CD73+core of tumor (CT), PD-L1+CT, and IDO+invasive margin (IM). ISLUSC 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-ISNSCLC patients with high-ISNSCLC 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 ISNSCLC was an independent indicator for prognosis. Finally, we combined ISNSCLC 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 ISLUAD and ISLUSC 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.AbbreviationsNSCLC, 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.