PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：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（TLSs），次级淋巴器官的类似物，引起了广泛的关注。然而,对BCBMs中TLS的潜在临床意义了解甚少。在这项研究中,我们评估了BCBM中TLS的密度和组成，并描述了其预后价值。
方法：收集98例患者（2015-2021年）的临床病理数据。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。免疫组织化学和多重免疫荧光（mIF）用于评估TLS异质性。
结果：在47例BCBM患者中发现了TLS。高TLS密度表明存活良好(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,三阴性乳腺癌亚型的OS延长（p=0.0482）。mIF结果显示滤泡辅助性T细胞（Tfh）的百分比存在显着差异，M2巨噬细胞，细胞毒性T淋巴细胞，和CD8+TIM-3+T淋巴细胞之间的TLS评分0-3（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，包含TLS评分和其他临床病理预测因子的新颖列线图显示了1年的突出可预测性，3年,和BCBMs的5年结局（曲线下面积>0.800）。
结论：我们的结果强调了TLS丰度对BCBM患者OS和PFS的影响。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。
方法：收集98例患者（2015-2021年）的临床病理数据。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。免疫组织化学和多重免疫荧光（mIF）用于评估TLS异质性。
结果：在47例BCBM患者中发现了TLS。高TLS密度表明存活良好(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,三阴性乳腺癌亚型的OS延长（p=0.0482）。mIF结果显示滤泡辅助性T细胞（Tfh）的百分比存在显着差异，M2巨噬细胞，细胞毒性T淋巴细胞，和CD8+TIM-3+T淋巴细胞之间的TLS评分0-3（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，包含TLS评分和其他临床病理预测因子的新颖列线图显示了1年的突出可预测性，3年,和BCBMs的5年结局（曲线下面积>0.800）。
结论：我们的结果强调了TLS丰度对BCBM患者OS和PFS的影响。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。
