Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types

Jasneet Kaur Khalsa, Nina Cheng, Joshua Keegan, Ameen Chaudry, Joseph Driver, Wenya Linda Bi, James Lederer and Khalid Shah ()
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Jasneet Kaur Khalsa: Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical School
Nina Cheng: Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical School
Joshua Keegan: Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School
Ameen Chaudry: Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical School
Joseph Driver: Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
Wenya Linda Bi: Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
James Lederer: Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School
Khalid Shah: Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17704-5

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