文章：

三级淋巴结构与免疫微环境特征在早期EGFR突变肺腺癌中的预后作用

The Prognostic Role of Tertiary Lymphoid Structures and Immune Microenvironment Signatures in Early-StageEGFR-Mutant Lung Adenocarcinoma

原文发布日期：17 July 2025

DOI: 10.3390/cancers17142379

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: The role of tertiary lymphoid structures (TLSs) in cancer prognosis is well established, yet their significance in early-stageEGFR-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-stageEGFR-mutant lung adenocarcinoma. Methods: 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. Results: High TLS density correlated with significantly longer DFS (43 vs. 20.5 months,p= 0.0082). No relationship was found between TLS density and PD-L1 TPS orEGFRmutation 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. Conclusions: In summary, TLS density is a potential prognostic biomarker for DFS in early-stageEGFR-mutant lung adenocarcinoma, independent of PD-L1 TPS orEGFRmutation subtype. Enhanced immune activation in high-TLS-density tumors highlights TLSs as a potential target for improving outcomes in these patients.

摘要翻译： 

背景/目的：三级淋巴结构（TLS）在癌症预后中的作用已得到广泛认可，但其在早期EGFR突变肺腺癌中的意义尚不明确。尽管早期肺癌的预后通常优于晚期，但复发仍是重大挑战。本研究探讨了TLS及其分子特征在早期EGFR突变肺腺癌中的预后价值。方法：采用多重免疫组化（IHC）技术识别肿瘤样本中的TLS并量化其密度，分析PD-L1肿瘤比例评分（TPS）和TLS密度与无病生存期（DFS）的关联。通过基因表达谱分析比较高、低TLS密度组间的肿瘤微环境特征。结果：高TLS密度与显著延长的DFS相关（43个月 vs. 20.5个月，p=0.0082）。TLS密度与PD-L1 TPS或EGFR突变亚型无显著关联。转录组分析显示高TLS密度组中免疫应答基因上调，包括参与T细胞和B细胞活化的相关基因；而低TLS密度肿瘤则呈现促进肿瘤生长的基因特征，如细胞周期和WNT通路激活。结论：TLS密度可作为早期EGFR突变肺腺癌DFS的潜在预后生物标志物，且独立于PD-L1 TPS或EGFR突变亚型。高TLS密度肿瘤中增强的免疫激活提示TLS可能成为改善此类患者预后的潜在干预靶点。

原文链接：

The Prognostic Role of Tertiary Lymphoid Structures and Immune Microenvironment Signatures in Early-StageEGFR-Mutant Lung Adenocarcinoma