Dataset Information

Single-cell spatial immune landscapes of primary and metastatic brain tumours.

ABSTRACT: Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment^1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues³. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.

SUBMITTER: Karimi E

PROVIDER: S-EPMC9931580 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Single-cell spatial immune landscapes of primary and metastatic brain tumours.

Karimi Elham E Yu Miranda W MW Maritan Sarah M SM Perus Lucas J M LJM Rezanejad Morteza M Sorin Mark M Dankner Matthew M Fallah Parvaneh P Doré Samuel S Zuo Dongmei D Fiset Benoit B Kloosterman Daan J DJ Ramsay LeeAnn L Wei Yuhong Y Lam Stephanie S Alsajjan Roa R Watson Ian R IR Roldan Urgoiti Gloria G Park Morag M Brandsma Dieta D Senger Donna L DL Chan Jennifer A JA Akkari Leila L Petrecca Kevin K Guiot Marie-Christine MC Siegel Peter M PM Quail Daniela F DF Walsh Logan A LA

Nature 20230201 7948

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment<sup>1,2</sup>, yet many single-cell studies lack spatial context and rely on dissociated tissues<sup>3</sup>. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma a ...[more]

PMID: 36725935

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Project description:BackgroundColorectal cancer (CRC) ranks as the second-leading cause of cancer-related death worldwide with metastases being the main cause of cancer-related death. Here, we investigated the genomic and transcriptomic alterations in matching adjacent normal tissues, primary tumors, and metastatic tumors of CRC patients.MethodsWe performed whole genome sequencing (WGS), multi-region whole exome sequencing (WES), simultaneous single-cell RNA-Seq, and single-cell targeted cDNA Sanger sequencing on matching adjacent normal tissues, primary tumors, and metastatic tumors from 12 metastatic colorectal cancer patients (n=84 for genomes, n=81 for exomes, n=9120 for single cells). Patient-derived tumor organoids were used to estimate the anti-tumor effects of a PPAR inhibitor, and self-renewal and differentiation ability of stem cell-like tumor cells.ResultsWe found that the PPAR signaling pathway was prevalently and aberrantly activated in CRC tumors. Blocking of PPAR pathway both suppressed the growth and promoted the apoptosis of CRC organoids in vitro, indicating that aberrant activation of the PPAR signaling pathway plays a critical role in CRC tumorigenesis. Using matched samples from the same patient, distinct origins of the metastasized tumors between lymph node and liver were revealed, which was further verified by both copy number variation and mitochondrial mutation profiles at single-cell resolution. By combining single-cell RNA-Seq and single-cell point mutation identification by targeted cDNA Sanger sequencing, we revealed important phenotypic differences between cancer cells with and without critical point mutations (KRAS and TP53) in the same patient in vivo at single-cell resolution.ConclusionsOur data provides deep insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution. Our findings offer novel knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy. The high-precision single-cell RNA-seq dataset of matched adjacent normal tissues, primary tumors, and metastases from CRCs may serve as a rich resource for further studies.

Dataset Information

Single-cell spatial immune landscapes of primary and metastatic brain tumours.

Publications

Single-cell spatial immune landscapes of primary and metastatic brain tumours.

Similar Datasets

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