Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types
Abstract Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Here, we generate distinct imageable syngeneic mouse GBM-tumor models and utilize RNA-sequencing, CyTOF and correlative immunohistochem...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2020-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-020-17704-5 |
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| author | Jasneet Kaur Khalsa Nina Cheng Joshua Keegan Ameen Chaudry Joseph Driver Wenya Linda Bi James Lederer Khalid Shah |
| author_facet | Jasneet Kaur Khalsa Nina Cheng Joshua Keegan Ameen Chaudry Joseph Driver Wenya Linda Bi James Lederer Khalid Shah |
| author_sort | Jasneet Kaur Khalsa |
| collection | DOAJ |
| description | Abstract Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Here, we generate distinct imageable syngeneic mouse GBM-tumor models and utilize RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identify immunologically-inert and -active syngeneic-tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells and resident macrophages; fewer eosinophils and SiglecF+ macrophages. To mimic the clinical-settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decreasing resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM-patients and mouse GBM-tumors show stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients. |
| format | Article |
| id | doaj-art-72c638431fd645f4b067eec34075de39 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2020-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-72c638431fd645f4b067eec34075de392025-08-20T03:21:03ZengNature PortfolioNature Communications2041-17232020-08-0111111410.1038/s41467-020-17704-5Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct typesJasneet Kaur Khalsa0Nina Cheng1Joshua Keegan2Ameen Chaudry3Joseph Driver4Wenya Linda Bi5James Lederer6Khalid Shah7Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Surgery, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Surgery, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical SchoolAbstract Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Here, we generate distinct imageable syngeneic mouse GBM-tumor models and utilize RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identify immunologically-inert and -active syngeneic-tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells and resident macrophages; fewer eosinophils and SiglecF+ macrophages. To mimic the clinical-settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decreasing resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM-patients and mouse GBM-tumors show stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients.https://doi.org/10.1038/s41467-020-17704-5 |
| spellingShingle | Jasneet Kaur Khalsa Nina Cheng Joshua Keegan Ameen Chaudry Joseph Driver Wenya Linda Bi James Lederer Khalid Shah Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types Nature Communications |
| title | Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types |
| title_full | Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types |
| title_fullStr | Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types |
| title_full_unstemmed | Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types |
| title_short | Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types |
| title_sort | immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types |
| url | https://doi.org/10.1038/s41467-020-17704-5 |
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