A novel tertiary lymphoid structure-associated signature accurately predicts patient prognosis and facilitates the selection of personalized treatment strategies for HNSCC

• DOI: 10.3389/fimmu.2025.1551844
• Publication Date: 2025-03-13T07:06:29Z
• Authors: Jinhao Zhang; Lu Zeng; Guobin Song; Gaoge Peng; Zhezheng Chen; Yamin Yuan; Taowu Chen; Tao Zhong; Shixi Chen; Zhengzhou Luo; Jingang Xiao; Lin Liu
• Keywords: nomogram; GSVA; Immunology; immunotherapy; Immunologic diseases. Allergy; RC581-607; tumour microenvironment; HNSCC; tertiary lymphatic structure

BackgroundHead and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer and is characterized by its aggressive nature and variable prognosis and response to immunotherapy. Tertiary lymphoid structures (TLSs) play crucial roles in creating a favourable immune microenvironment to control tumour progression. However, the specific impact of these structures on HNSCC has not been thoroughly studied.MethodsIn this study, a comprehensive review of tertiary lymphoid structures was conducted by analysing 9 TLS-associated genes in a cohort of 871 HNSCC patients. Distinct TLS-related subgroups were identified through unsupervised clustering analysis, and the associated genes were explored. Prognostic genes were identified via univariate Cox and Boruta algorithms, and a novel TLS-related scoring system was developed via the GSVA algorithm.ResultsOur study revealed that patients with higher TLS-related scores had improved overall survival and were more likely to benefit from immunotherapy. Furthermore, we observed a significant negative correlation between sensitivity to traditional chemotherapeutic agents and the TLS-related signature score.ConclusionsOur findings suggest that the TLS-related features of HNSCC patients hold promise as predictive indicators for immunotherapy efficacy and may offer novel insights for tailoring personalized treatment strategies in clinical practice.