The Prognostic Role of Tertiary Lymphoid Structures and Immune Microenvironment Signatures in Early-Stage -Mutant Lung Adenocarcinoma.
Journal
Cancers
Journal Volume
17
Journal Issue
14
Start Page
Article number 2379
ISSN
2072-6694
Date Issued
2025-07-17
Author(s)
Abstract
The 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.
Subjects
EGFR-mutant lung adenocarcinoma
disease-free survival
tertiary lymphoid structure
tumor immune microenvironment
SDGs
Type
journal article