Hsu, Wei-HsunWei-HsunHsuHsu, Chia-ChiChia-ChiHsuHsieh, Min-ShuMin-ShuHsiehCHIH-HSIN YANG2025-08-082025-08-082025-07-17https://scholars.lib.ntu.edu.tw/handle/123456789/731130The role of tertiary lymphoid structures (TLSs) in cancer prognosis is well established, yet their significance in early-stage -mutant lung adenocarcinoma remains unclear. While outcomes for early-stage lung cancer are generally better than those of late-stage disease, recurrence remains a significant challenge. This study investigates the prognostic value of TLSs and their molecular characteristics in early-stage -mutant lung adenocarcinoma.TLSs were identified in tumor samples using multiplex immunohistochemistry (IHC), and their density was quantified. The PD-L1 tumor proportion score (TPS) and TLS density were analyzed for associations with disease-free survival (DFS). Gene expression profiling was performed to compare tumor microenvironment signatures between high- and low-TLS-density groups.High TLS density correlated with significantly longer DFS (43 vs. 20.5 months, = 0.0082). No relationship was found between TLS density and PD-L1 TPS or mutation subtype. Transcriptomic analysis revealed upregulated immune response genes in the high-TLS-density group, including those involved in T and B cell activation. Low-TLS-density tumors exhibited gene signatures promoting tumor growth, such as cell cycle and WNT pathway activation.In summary, TLS density is a potential prognostic biomarker for DFS in early-stage -mutant lung adenocarcinoma, independent of PD-L1 TPS or mutation subtype. Enhanced immune activation in high-TLS-density tumors highlights TLSs as a potential target for improving outcomes in these patients.enEGFR-mutant lung adenocarcinomadisease-free survivaltertiary lymphoid structuretumor immune microenvironment[SDGs]SDG3journal article10.3390/cancers1714237940723259