Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation
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 si...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/92678 |
| _version_ | 1797383121240326144 |
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| author | Philip Schmassmann Julien Roux Steffen Dettling Sabrina Hogan Tala Shekarian Tomás A Martins Marie-Françoise Ritz Sylvia Herter Marina Bacac Gregor Hutter |
| author_facet | Philip Schmassmann Julien Roux Steffen Dettling Sabrina Hogan Tala Shekarian Tomás A Martins Marie-Françoise Ritz Sylvia Herter Marina Bacac Gregor Hutter |
| author_sort | Philip Schmassmann |
| collection | DOAJ |
| description | 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 regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease. |
| first_indexed | 2024-03-08T21:15:13Z |
| format | Article |
| id | doaj.art-5a6642576293437db6f6762c4cadf0eb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-08T21:15:13Z |
| publishDate | 2023-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5a6642576293437db6f6762c4cadf0eb2023-12-21T19:34:28ZengeLife Sciences Publications LtdeLife2050-084X2023-12-011210.7554/eLife.92678Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activationPhilip Schmassmann0https://orcid.org/0000-0002-9411-3852Julien Roux1https://orcid.org/0000-0002-4192-5099Steffen Dettling2Sabrina Hogan3https://orcid.org/0000-0003-3994-8109Tala Shekarian4Tomás A Martins5https://orcid.org/0000-0001-6016-2288Marie-Françoise Ritz6https://orcid.org/0000-0002-5650-9987Sylvia Herter7Marina Bacac8Gregor Hutter9Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, SwitzerlandBioinformatics Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Roche Innovation Center Munich, Penzberg, GermanyBrain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, SwitzerlandBrain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, SwitzerlandBrain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, SwitzerlandBrain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, SwitzerlandRoche Pharmaceutical Research and Early Development, Roche Innovation Center Zürich, Schlieren, SwitzerlandRoche Pharmaceutical Research and Early Development, Roche Innovation Center Zürich, Schlieren, SwitzerlandBrain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland; Department of Neurosurgery, University Hospital Basel, Basel, SwitzerlandGlioblastoma (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 regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease.https://elifesciences.org/articles/92678glioblastomatumor microenvironmentscRNAseq |
| spellingShingle | Philip Schmassmann Julien Roux Steffen Dettling Sabrina Hogan Tala Shekarian Tomás A Martins Marie-Françoise Ritz Sylvia Herter Marina Bacac Gregor Hutter Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation eLife glioblastoma tumor microenvironment scRNAseq |
| title | Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation |
| title_full | Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation |
| title_fullStr | Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation |
| title_full_unstemmed | Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation |
| title_short | Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation |
| title_sort | single cell characterization of human gbm reveals regional differences in tumor infiltrating leukocyte activation |
| topic | glioblastoma tumor microenvironment scRNAseq |
| url | https://elifesciences.org/articles/92678 |
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