Tertiary Lymphoid Structures Predict Prognosis and Immune Checkpoint Inhibitor Efficacy in Lung Squamous Cell Carcinoma.

Abstract

Lung squamous cell carcinoma (LUSC) is a highly mortal cancer. Tertiary lymphoid structures (TLSs) play a crucial role in creating a specific and essential environment for the development of cellular and humoral immune responses against tumours. This study investigated the effect of TLSs on prognosis and the prediction of immunotherapy efficacy in LUSC. To investigate the association between TLSs and clinicopathological features, haematoxylin and eosin staining and multiple immunofluorescence staining were performed. A comparative examination of survival and the factors influencing it was carried out between the TLS-/+, high and low TLS density, immature tertiary lymphoid structures (imTLS) and mature tertiary lymphoid structures (mTLS) groups of patients. To further analyse the prognostic value of TLSs in the immunotherapy cohort of patients with LUSC, two hundred and ninety-seven patients with LUSC were enrolled in this study. Of these, 129 patients were harbouring TLS+. Cramer's V relationships analysis revealed that both Stage (p = 0.029) and PD-L1 ≥ 50% (p = 0.011) were significant predictors of TLS+. Cox proportional hazards model multivariate analysis showed that the TLS+ (p = 0.037), high TLS density (p = 0.014) and mTLS (p = 0.001) were associated with better overall survival (OS) in LUSC patients. Multivariate analyses confirmed that TLS+ was an independent prognostic predictor for OS in the LUSC immunotherapy cohort (p = 0.021). This study provided evidence that LUSC patients with TLS+, high TLS density and mTLS had a favourable prognosis, suggesting that TLSs are an independent positive prognostic factor for LUSC patients.