乳腺癌脑转移（BCBM）患者的生活质量迅速下降。最近，三级淋巴结构（TLS）作为二级淋巴器官的类似物，引起了广泛的关注。然而，人们对 TLS 在 BCBM 中的潜在临床意义知之甚少。在本研究中，我们评估了 BCBM 中 TLS 的密度和组成，并描述了其预后价值。收集了 98 名患者（2015-2021 年）的临床病理数据。对 TLS 进行了评估，并构建了 TLS 评分系统。使用Kaplan-Meier方法计算组间无进展生存期（PFS）和总生存期（OS）的差异。使用免疫组织化学和多重免疫荧光 (mIF) 评估 TLS 异质性。在 47 名 BCBM 患者中鉴定出 TLS。高 TLS 密度表明生存良好（OS，p=0.003；PFS，p<0.001）。在人表皮生长因子受体 2 型阳性亚型中，TLS 与 OS (p=0.0172) 和 PFS (p=0.0161) 呈正相关，在三阴性乳腺癌亚型中与 OS 延长 (p=0.0482) 呈正相关。 mIF结果显示，TLS评分0-3组之间滤泡辅助T（Tfh）细胞、M2巨噬细胞、细胞毒性T淋巴细胞和CD8 TIM-3 T淋巴细胞的百分比存在显着差异（细胞毒性T淋巴细胞，p=0.044； Tfh，p=0.021；M2 巨噬细胞，p=0.033；CD8 TIM-3 T 淋巴细胞，p=0.018）。此外，结合了 TLS 评分和其他临床病理学预测因子的新型列线图显示了 BCBM 的 1 年、3 年和 5 年结果的显着可预测性（曲线下面积 >0.800）。我们的结果强调了 TLS 丰度对 BCBM 的影响。 BCBM 患者的 OS 和 PFS。此外，我们描述了 TLS 的免疫组成，并提出了新的列线图来预测 BCBM 患者的预后。© 作者（或其雇主）2024。在 CC BY-NC 下允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Patients with breast cancer brain metastases (BCBM) experience a rapid decline in their quality of life. Recently, tertiary lymphoid structures (TLSs), analogs of secondary lymphoid organs, have attracted extensive attention. However, the potential clinical implications of TLSs in BCBMs are poorly understood. In this study, we evaluated the density and composition of TLSs in BCBMs and described their prognostic value.Clinicopathological data were collected from 98 patients (2015-2021). TLSs were evaluated, and a TLS scoring system was constructed. Differences in progression-free survival (PFS) and overall survival (OS) between groups were calculated using the Kaplan-Meier method. Immunohistochemistry and multiplex immunofluorescence (mIF) were used to assess TLSs heterogeneity.TLSs were identified in 47 patients with BCBM. High TLSs density indicated favorable survival (OS, p=0.003; PFS, p<0.001). TLS was positively associated with OS (p=0.0172) and PFS (p=0.0161) in the human epidermal growth factor receptor type 2-positive subtype, and with prolonged OS (p=0.0482) in the triple-negative breast cancer subtype. The mIF results showed significant differences in the percentages of T follicular helper (Tfh) cells, M2 macrophages, cytotoxic T lymphocytes, and CD8+TIM-3+ T lymphocytes between the groups of TLS scores 0-3 (cytotoxic T lymphocytes, p=0.044; Tfh, p=0.021; M2 macrophages, p=0.033; CD8+TIM-3+ T lymphocytes, p=0.018). Furthermore, novel nomograms incorporating the TLS scores and other clinicopathological predictors demonstrated prominent predictability of the 1-year, 3-year, and 5-year outcomes of BCBMs (area under the curve >0.800).Our results highlight the impact of TLSs abundance on the OS and PFS of patients with BCBM. Additionally, we described the immune composition of TLSs and proposed novel nomograms to predict the prognosis of patients with BCBM.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.