脑转移瘤中三级淋巴结构的鉴定与特征分析
Identification and characterization of tertiary lymphoid structures in brain metastases.
作者信息
Mughal Sadaf S, Reiss Yvonne, Felsberg Jörg, Meyer Lasse, Macas Jadranka, Schlue Silja, Starzetz Tatjana, Köhrer Karl, Fehm Tanja, Müller Volkmar, Lamszus Katrin, Schadendorf Dirk, Helfrich Iris, Wikman Harriet, Berghoff Anna, Brors Benedikt, Plate Karl H, Reifenberger Guido
机构信息
Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
German Cancer Consortium (DKTK), Core Center Heidelberg, 69120, Heidelberg, Germany.
出版信息
Acta Neuropathol Commun. 2025 May 3;13(1):91. doi: 10.1186/s40478-025-02007-x.
Brain metastases (BrM) are the most common cancers in the brain and linked to poor prognosis. Given the high incidence and often limited treatment options, understanding the complexity of the BrM tumor microenvironment is crucial for the development of novel therapeutic strategies. We performed transcriptome-wide gene expression profiling combined with spatial immune cell profiling to characterize the tumor immune microenvironment in 95 patients with BrM from different primary tumors. We found that BrM from lung carcinoma and malignant melanoma showed overall higher immune cell infiltration as compared to BrM from breast carcinoma. RNA sequencing-based immune cell deconvolution revealed gene expression signatures indicative of tertiary lymphoid structures (TLS) in subsets of BrM, mostly from lung cancer and melanoma. This finding was corroborated by multiplex immunofluorescence staining of immune cells in BrM tissue sections. Detection of TLS signatures was more common in treatment-naïve BrM and associated with prolonged survival after BrM diagnosis in lung cancer patients. Our findings highlight the cellular diversity of the tumor immune microenvironment in BrM of different cancer types and suggest a role of TLS formation for BrM patient outcome.
脑转移瘤(BrM)是脑部最常见的癌症,且与预后不良相关。鉴于其高发病率以及治疗选择往往有限,了解BrM肿瘤微环境的复杂性对于开发新的治疗策略至关重要。我们进行了全转录组基因表达谱分析,并结合空间免疫细胞谱分析,以表征95例来自不同原发肿瘤的BrM患者的肿瘤免疫微环境。我们发现,与来自乳腺癌的BrM相比,来自肺癌和恶性黑色素瘤的BrM总体上显示出更高的免疫细胞浸润。基于RNA测序的免疫细胞反卷积揭示了BrM亚组中指示三级淋巴结构(TLS)的基因表达特征,这些亚组大多来自肺癌和黑色素瘤。BrM组织切片中免疫细胞的多重免疫荧光染色证实了这一发现。TLS特征的检测在未经治疗的BrM中更为常见,并且与肺癌患者BrM诊断后的生存期延长相关。我们的研究结果突出了不同癌症类型的BrM中肿瘤免疫微环境的细胞多样性,并提示TLS形成对BrM患者预后的作用。