在几种实体肿瘤中，三级淋巴结结构（TLS）在决定预后和免疫治疗反应中起关键作用。然而，基于癌症基因组图谱（TCGA）队列的TLS相关基因签名对于乳腺癌（BRCA）患者的影响仍存在争议。基于TCGA-BRCA数据集（n=866），我们鉴定出一个9基因的TLS签名，并进一步分析其预后价值。然后，我们探讨了TLS签名与分子亚型、免疫微环境、肿瘤突变负荷（TMB）之间的关系。高TLS签名患者的总体生存率（OS）比低TLS签名患者更好，这与METABRIC队列的结果一致。多变量分析显示TLS签名在OS方面仍然是一个独立的预后指标。此外，我们建立了一个图表，将TLS签名和其他独立变量集成，以预测个体死亡风险。综合结果显示，高TLS签名的患者从免疫治疗中获益；该签名还与细胞增殖通路抑制、低TP53突变率、B细胞、CD8+T细胞、CD4+T细胞和M1巨噬细胞的高浸润有关。因此，TLS签名是区分乳腺癌预后和免疫微环境的有希望的生物标志物。© 2023. Springer Nature Limited.

Tertiary lymphoid structures (TLSs) play a crucial role in determining prognosis and response to immunotherapy in several solid malignancies. Nevertheless, the effect of TLS-associated gene signature based on The Cancer Genome Atlas (TCGA) cohort in patients with breast cancer (BRCA) remains controversial. Based on TCGA-BRCA dataset (n = 866), 9-gene was identified to construct an TLS signature and further analyzed its prognostic value. Then, we explored the relationship of this TLS signature with molecular subtype, immune microenvironment, tumor mutational burden (TMB). High-TLS signature patients had a better overall survival (OS) than low-TLS signature patients, consistent with the results in the METABRIC cohort. Multivariate analysis revealed that TLS signature remained an independent prognostic indicator for OS. In addition, we established a nomogram with the integration of TLS signature and other independent variables to predict individual risk of death. The comprehensive results showed that patients with high TLS signature benefit from immunotherapy; the signature was also correlated with inhibition of cell proliferation pathways, low TP53 mutation rate, high infiltration of B cells, CD8 + T cells, CD4 + T cells, and M1 macrophages. Therefore, TLS signature is a promising biomarker to distinguish the prognosis and immune microenvironment in BRCA.© 2023. Springer Nature Limited.