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

Elham Karimi, Miranda W. Yu, Sarah M. Maritan, Lucas J. M. Perus, Morteza Rezanejad, Mark Sorin, Matthew Dankner, Parvaneh Fallah, Samuel Doré, Dongmei Zuo, Benoit Fiset, Daan J. Kloosterman, LeeAnn Ramsay, Yuhong Wei, Stephanie Lam, Roa Alsajjan, Ian R. Watson, Gloria Roldan Urgoiti, Morag Park, Dieta Brandsma, Donna L. Senger, Jennifer A. Chan, Leila Akkari, Kevin Petrecca, Marie-Christine Guiot, Peter M. Siegel (), Daniela F. Quail () and Logan A. Walsh ()
Additional contact information
Elham Karimi: McGill University
Miranda W. Yu: McGill University
Sarah M. Maritan: McGill University
Lucas J. M. Perus: McGill University
Morteza Rezanejad: University of Toronto
Mark Sorin: McGill University
Matthew Dankner: McGill University
Parvaneh Fallah: McGill University
Samuel Doré: McGill University
Dongmei Zuo: McGill University
Benoit Fiset: McGill University
Daan J. Kloosterman: Netherlands Cancer Institute
LeeAnn Ramsay: McGill University
Yuhong Wei: McGill University
Stephanie Lam: McGill University
Roa Alsajjan: King Saud University College of Medicine
Ian R. Watson: McGill University
Gloria Roldan Urgoiti: University of Calgary
Morag Park: McGill University
Dieta Brandsma: Antoni van Leeuwenhoek Hospital
Donna L. Senger: McGill University
Jennifer A. Chan: University of Calgary
Leila Akkari: Netherlands Cancer Institute
Kevin Petrecca: McGill University
Marie-Christine Guiot: McGill University
Peter M. Siegel: McGill University
Daniela F. Quail: McGill University
Logan A. Walsh: McGill University

Nature, 2023, vol. 614, issue 7948, 555-563

Abstract: 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 microenvironment1,2, 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.

Date: 2023
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DOI: 10.1038/s41586-022-05680-3

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