4.6 Article

Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors

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CELL REPORTS MEDICINE
卷 4, 期 1, 页码 -

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CELL PRESS
DOI: 10.1016/j.xcrm.2022.100900

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Brain metastases (BrMs) are a common type of brain tumor in adults, usually originating from lung and breast primary cancers. Effective therapies are needed due to the high mortality rate associated with BrMs. Genetic profiling of primary tumors is used to guide targeted therapies against BrMs, and immune-based strategies for metastatic cancer treatment are gaining momentum. However, the tumor immune microenvironment (TIME) of BrMs is heterogeneous and it is unknown whether specific genetic profiles are associated with distinct immune states. In this study, the immunogenomic landscape of human BrMs was extensively characterized, revealing unique TIME phenotypes in genetically distinct lung- and breast-BrMs, which allows for the development of personalized immunotherapies based on the genetic makeup of the tumors.
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 tar-geted therapies against BrMs, and immune-based strategies for the treatment of metastatic cancer are gain-ing 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 genet-ically distinct lung-and breast-BrMs, thereby enabling the development of personalized immunotherapies tailored by the genetic makeup of the tumors.

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