Similar Datasets
Project description:Breast cancer brain metastases (BCBM) are a severe condition with high demand for improved personalized treatment, but a comprehensive understanding of BCBM immune-microenvironment heterogeneity and susceptibility to immunotherapy is lacking. Here, we multimodally profile the immune niche in a vast, clinically well-annotated cohort of 156 BCBM applying tissue cytometry, bulk and single nuclei RNA-sequencing, flow cytometry, and spatial transcriptomics, complemented by functional studies in patient-derived models. Integrative analyses reveal two immune landscapes predicting prolonged patient survival and not deducible from paired primary tumors: 1) BCBM with a high proportion of CD8 tissue-resident-like memory T cells as major players of tumor immune control. 2) BCBM containing tertiary lymphoid structures. Surrogate signatures of these landscapes are prognostic in independent BCBM and primary breast cancer cohorts, are associated with fewer metastases, and predict immunotherapy response. Our work provides critical insights into anti-tumor immunity in BCBM and identifies novel biomarkers with translational relevance.
2026-03-10 | GSE324453 | GEO
Project description:Breast cancer brain metastases (BCBM) are a severe condition with high demand for improved personalized treatment, but a comprehensive understanding of BCBM immune-microenvironment heterogeneity and susceptibility to immunotherapy is lacking. Here, we multimodally profile the immune niche in a vast, clinically well-annotated cohort of 156 BCBM applying tissue cytometry, bulk and single nuclei RNA-sequencing, flow cytometry, and spatial transcriptomics, complemented by functional studies in patient-derived models. Integrative analyses reveal two immune landscapes predicting prolonged patient survival and not deducible from paired primary tumors: 1) BCBM with a high proportion of CD8 tissue-resident-like memory T cells as major players of tumor immune control. 2) BCBM containing tertiary lymphoid structures. Surrogate signatures of these landscapes are prognostic in independent BCBM and primary breast cancer cohorts, are associated with fewer metastases, and predict immunotherapy response. Our work provides critical insights into anti-tumor immunity in BCBM and identifies novel biomarkers with translational relevance.
2026-03-10 | GSE322943 | GEO
Project description:Dissecting the cellular architecture of breast cancer brain metastases reveals prognostically distinct immune landscapes
| PRJNA1435156 | ENA
Project description:Dissecting the cellular architecture of breast cancer brain metastases reveals prognostically distinct immune landscapes [RNA-Seq]
| PRJNA1431999 | ENA
Project description:Dissecting the cellular architecture of breast cancer brain metastases reveals prognostically distinct immune landscapes [snRNA-Seq]
| PRJNA1435165 | ENA
Project description:Brain metastasis (BrM) is the most common form of brain cancer, characterized by neurologic disability and an abysmal prognosis. Unfortunately, our understanding of the biology underlying human BrMs remains rudimentary. Here, we present an integrative analysis of >100,000 malignant and non-malignant cells from 15 human parenchymal BrMs, generated by single-cell transcriptomics, mass cytometry, and complemented with mouse model- and in silico approaches. We interrogated the composition of BrM niches, molecularly defined the blood-tumor interface, and revealed stromal immunosuppressive states enriched with infiltrated T cells and macrophages. Specific single-cell interrogation of metastatic tumor cells provides a framework of 8 functional cell programs that coexist or anticorrelate. Collectively, these programs delineate two functional BrM archetypes, one proliferative and the other inflammatory, that are evidently shaped through tumor-immune interactions. Our resource provides a foundation to understand the molecular basis of BrM in patients with tumor cell-intrinsic and host environmental traits.
| S-EPMC8857062 | biostudies-literature
Project description: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.
| S-EPMC9873981 | biostudies-literature
Project description:Here we present an integrative analysis of 15 human parenchymal BrMs as a resource, generated by single-cell transcriptomics, and complemented with two mouse models- and in silico- approaches. We interrogated the composition of BrM niches, molecularly defined the blood-tumor interface, and reveal stromal immunosuppressive states, enriched with infiltrated T cells and macrophages. Specific single-cell interrogation of metastatic tumor cells provides a novel framework of 8 functional cell programs that coexist or anticorrelate. Collectively, these programs delineate two functional BrM archetypes, one proliferative and the other inflammatory, that are evidently shaped through tumor-immune interactions. Our resource provides a foundation to understand the molecular basis of BrM in patients with tumor cell-intrinsic and host environmental- traits.
2021-11-12 | GSE186344 | GEO
Project description:Cellular Architecture of Human Brain Metastases
| PRJNA773428 | ENA
Project description:Background-Triple-negative breast cancer is a prevalent breast cancer subtype with the lowest 5-year survival. Several factors contribute to its treatment response, but the inherent molecular and cellular tumor heterogeneity are increasingly acknowledged as crucial determinants.Methods-Spatial transcriptomic profiling was performed on FFPE tissues from a retrospective, treatment-naive group of women with differential prognoses (17 with >15 years survival- good prognosis (GPx) and 15 with <3 years survival-poor prognosis (PPx)) using GeoMX® Digital Spatial Profiler. Regions of interest were segmented on pan-cytokeratin and analyzed for tumor and stromal components, probed using GeoMx human whole transcriptome atlas (WTA) panel. Data quality control, normalization, and differential analysis was performed in R using GeomxTools and linear mixed models. Additional analyses including cell-type deconvolution, spatial entropy, functional enrichment, TF-target / ligand-receptor analysis and convolution neural networks were employed to identify significant gene signatures contributing to differential prognosis.Results-Here we report on the spatial and molecular heterogeneity underlying differential prognosis. We observe that the state of the epithelia and its microenvironment (TME) are transcriptionally distinct between the two groups. Invasive epithelia in GPx show a significant increase in immune transcripts with the TME exhibiting increased immune cell presence (via IF), while in PPx they are more metabolically and translationally active, with the TME being more mesenchymal/fibrotic. Specifically, pre-cancerous epithelia in PPx display a prescience of aggressiveness as evidenced by increased EMT-signaling. We identify distinct epithelial gene signatures for PPx and GPx, that can, with high accuracy, classify samples at the time of diagnosis and likely inform therapy.Conclusions-To the best of our knowledge, this is the first study to leverage spatial transcriptomics for an in-depth delineation of the cellular and molecular underpinnings of differential prognosis in TNBC. Our study highlights the potential of spatial transcriptomics to not only uncover the molecular drivers of differential prognosis in TNBC but also to pave the way for precision diagnostics and tailored therapeutic strategies, transforming the clinical landscape for this aggressive breast cancer subtype.
| S-EPMC11844391 | biostudies-literature