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Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation

View ORCID ProfilePhilip Schmassmann, View ORCID ProfileJulien Roux, Steffen Dettling, Sabrina Hogan, Tala Shekarian, Tomás A. Martins, Marie-Françoise Ritz, Sylvia Herter, Marina Bacac, View ORCID ProfileGregor Hutter
doi: https://doi.org/10.1101/2022.06.17.496574
Philip Schmassmann
1Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland
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  • For correspondence: p.schmassmann@unibas.ch gregor.hutter@usb.ch
Julien Roux
2Bioinformatics Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland
3Swiss Institute of Bioinformatics, Basel, Switzerland
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Steffen Dettling
4Roche Pharmaceutical Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
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Sabrina Hogan
1Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland
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Tala Shekarian
1Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland
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Tomás A. Martins
1Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland
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Marie-Françoise Ritz
1Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland
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Sylvia Herter
5Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zürich, Schlieren, Switzerland
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Marina Bacac
5Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zürich, Schlieren, Switzerland
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Gregor Hutter
1Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland
6Department of Neurosurgery, University Hospital Basel, Basel, Switzerland
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  • ORCID record for Gregor Hutter
  • For correspondence: p.schmassmann@unibas.ch gregor.hutter@usb.ch
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Abstract

Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis of > 45’000 cells, we revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation signature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8+ T cells with circulating cells identified CX3CR1high and CX3CR1int CD8+ T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Tumor CD8+ T cells displayed a tissue-resident memory phenotype with dysfunctional features. Our analysis provides a large-scale dissection of GBM-associated leukocytes, serving as a reference map of human GBM-TME.

Competing Interest Statement

Gregor Hutter has equity in, and is a cofounder of Incephalo Inc. All other authors declare they have no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 19, 2022.
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Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation
Philip Schmassmann, Julien Roux, Steffen Dettling, Sabrina Hogan, Tala Shekarian, Tomás A. Martins, Marie-Françoise Ritz, Sylvia Herter, Marina Bacac, Gregor Hutter
bioRxiv 2022.06.17.496574; doi: https://doi.org/10.1101/2022.06.17.496574
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Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation
Philip Schmassmann, Julien Roux, Steffen Dettling, Sabrina Hogan, Tala Shekarian, Tomás A. Martins, Marie-Françoise Ritz, Sylvia Herter, Marina Bacac, Gregor Hutter
bioRxiv 2022.06.17.496574; doi: https://doi.org/10.1101/2022.06.17.496574

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