Abstract：
OBJECTIVE: The prognosis of patients with brain metastases (BMs) originating from lung cancer remains poor, despite advancements in treatment strategies. The role of tertiary lymphoid structures (TLSs) within the tumor immune microenvironment of BMs has not been extensively explored.
METHODS: This study utilized patient-derived clinical samples from 17 patients with histologically confirmed BMs of lung cancer, undergoing surgical resection. Immunohistochemistry was employed to analyze the presence and characteristics of TLS and tumor-infiltrating lymphocytes (TILs) within BM tissues, correlating these with clinical outcomes.
RESULTS: TLSs, albeit in their immature form, were identified within BM tissues, distinguishing them from their mature counterparts in primary lung cancer tissues. A significant correlation between TLS density (but not TIL density) and improved postoperative survival was observed, underscoring the potential of TLS density as an independent prognostic marker. Furthermore, TLS density did not correlate with the Graded Prognostic Assessment (GPA) index, suggesting its unique prognostic value beyond conventional predictors.
CONCLUSIONS: Our findings reveal the presence of TLSs in lung cancer-derived BMs and highlight their prognostic significance, independent of the GPA index. The identification of TLS within the unique central nervous system tumor microenvironment offers new insights into the immune landscape of BMs and suggests potential avenues for immunotherapeutic interventions targeting these structures to improve patient outcomes.
METHODS: This study utilized patient-derived clinical samples from 17 patients with histologically confirmed BMs of lung cancer, undergoing surgical resection. Immunohistochemistry was employed to analyze the presence and characteristics of TLS and tumor-infiltrating lymphocytes (TILs) within BM tissues, correlating these with clinical outcomes.
RESULTS: TLSs, albeit in their immature form, were identified within BM tissues, distinguishing them from their mature counterparts in primary lung cancer tissues. A significant correlation between TLS density (but not TIL density) and improved postoperative survival was observed, underscoring the potential of TLS density as an independent prognostic marker. Furthermore, TLS density did not correlate with the Graded Prognostic Assessment (GPA) index, suggesting its unique prognostic value beyond conventional predictors.
CONCLUSIONS: Our findings reveal the presence of TLSs in lung cancer-derived BMs and highlight their prognostic significance, independent of the GPA index. The identification of TLS within the unique central nervous system tumor microenvironment offers new insights into the immune landscape of BMs and suggests potential avenues for immunotherapeutic interventions targeting these structures to improve patient outcomes.
摘要：
目的：肺癌脑转移（BMs）患者预后较差，尽管治疗策略有所进步。三级淋巴结构（TLSs）在BM的肿瘤免疫微环境中的作用尚未得到广泛研究。
方法：本研究利用了17例经组织学证实的肺癌患者的临床样本，正在接受手术切除。免疫组织化学用于分析BM组织中TLS和肿瘤浸润淋巴细胞（TIL）的存在和特征，将这些与临床结果相关联。
结果：TLS，尽管形式不成熟，在BM组织中被鉴定出来，将它们与原发性肺癌组织中的成熟对应物区分开。观察到TLS密度（而非TIL密度）与术后生存率改善之间存在显着相关性，强调TLS密度作为独立预后标志物的潜力。此外，TLS密度与分级预后评估（GPA）指数无关，表明其超越传统预测因子的独特预后价值。
结论：我们的发现揭示了肺癌来源的BMs中存在TLS，并强调了其预后意义。独立于GPA指数。在独特的中枢神经系统肿瘤微环境中鉴定TLS提供了对BM免疫景观的新见解，并提出了针对这些结构的免疫治疗干预以改善患者预后的潜在途径。
方法：本研究利用了17例经组织学证实的肺癌患者的临床样本，正在接受手术切除。免疫组织化学用于分析BM组织中TLS和肿瘤浸润淋巴细胞（TIL）的存在和特征，将这些与临床结果相关联。
结果：TLS，尽管形式不成熟，在BM组织中被鉴定出来，将它们与原发性肺癌组织中的成熟对应物区分开。观察到TLS密度（而非TIL密度）与术后生存率改善之间存在显着相关性，强调TLS密度作为独立预后标志物的潜力。此外，TLS密度与分级预后评估（GPA）指数无关，表明其超越传统预测因子的独特预后价值。
结论：我们的发现揭示了肺癌来源的BMs中存在TLS，并强调了其预后意义。独立于GPA指数。在独特的中枢神经系统肿瘤微环境中鉴定TLS提供了对BM免疫景观的新见解，并提出了针对这些结构的免疫治疗干预以改善患者预后的潜在途径。
