Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Neuroscience Research Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Cell Rep Med. 2023 Jan 17;4(1):100900. doi: 10.1016/j.xcrm.2022.100900.
Brain metastases (BrMs) are the most common form of brain tumors in adults and frequently originate from lung and breast primary cancers. BrMs are associated with high mortality, emphasizing the need for more effective therapies. Genetic profiling of primary tumors is increasingly used as part of the effort to guide targeted therapies against BrMs, and immune-based strategies for the treatment of metastatic cancer are gaining momentum. However, the tumor immune microenvironment (TIME) of BrM is extremely heterogeneous, and whether specific genetic profiles are associated with distinct immune states remains unknown. Here, we perform an extensive characterization of the immunogenomic landscape of human BrMs by combining whole-exome/whole-genome sequencing, RNA sequencing of immune cell populations, flow cytometry, immunofluorescence staining, and tissue imaging analyses. This revealed unique TIME phenotypes in genetically distinct lung- and breast-BrMs, thereby enabling the development of personalized immunotherapies tailored by the genetic makeup of the tumors.
脑转移瘤（BrMs）是成年人中最常见的脑肿瘤形式，通常源自肺癌和乳腺癌等原发性癌症。BrMs 死亡率较高，这强调了需要更有效的治疗方法。对原发性肿瘤进行基因谱分析越来越多地被用于指导针对 BrMs 的靶向治疗，并且针对转移性癌症的免疫治疗策略也在不断发展。然而，脑转移瘤的肿瘤免疫微环境（TIME）极其异质，特定的基因谱是否与不同的免疫状态相关仍然未知。在这里，我们通过结合全外显子/全基因组测序、免疫细胞群体的 RNA 测序、流式细胞术、免疫荧光染色和组织成像分析，对人类 BrMs 的免疫基因组景观进行了广泛的描述。这揭示了具有独特 TIME 表型的不同遗传特征的肺癌和乳腺癌脑转移瘤，从而能够根据肿瘤的遗传构成开发出个性化的免疫疗法。
