Department of Neurosurgery, Nagoya University Faculty of Medicine, Nagoya, Japan.
Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Anticancer Res. 2024 Aug;44(8):3615-3621. doi: 10.21873/anticanres.17184.
BACKGROUND/AIM: 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.
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.
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.
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.
背景/目的：尽管治疗策略有所进步，源自肺癌的脑转移瘤（BMs）患者的预后仍然很差。BMs 肿瘤免疫微环境中的三级淋巴结构（TLSs）的作用尚未得到广泛探索。
本研究利用了 17 名经组织学证实的肺癌 BMs 手术切除患者的临床样本。免疫组化用于分析 BM 组织中 TLS 和肿瘤浸润淋巴细胞（TILs）的存在和特征，并将其与临床结果相关联。
在 BM 组织中发现了 TLS（尽管处于不成熟形式），与原发性肺癌组织中的成熟 TLS 区分开来。TLS 密度（而非 TIL 密度）与术后生存改善显著相关，这突出了 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，表明其具有超越传统预测因子的独特预后价值。
我们的研究结果表明，TLS 存在于肺癌衍生的 BMs 中，并强调了其独立于 GPA 指数的预后意义。在独特的中枢神经系统肿瘤微环境中鉴定出 TLS 为 BMs 的免疫景观提供了新的见解，并提示了针对这些结构进行免疫治疗干预以改善患者预后的潜在途径。
