2. Academic Validation
  3. Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas

Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas

  • Neuro Oncol. 2021 Nov 2;23(11):1922-1935. doi: 10.1093/neuonc/noab075.
Jacky Yeung 1,  Vesal Yaghoobi 2,  Danielle Miyagishima 1,  Matthew D Vesely 3 4,  Tianxiang Zhang 4,  Ti Badri 4,  Ala Nassar 4,  Xue Han 4,  Miguel F Sanmamed 4 5,  Mark Youngblood 6,  Matthieu Peyre 7,  Michel Kalamarides 7,  David L Rimm 2,  Murat Gunel 1,  Lieping Chen 4
Affiliations

Affiliations

  • 1 Department of Neurological Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 2 Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 3 Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 4 Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 5 Program of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
  • 6 Department of Neurosurgery, Northwestern University School of Medicine, Chicago, Illinois, USA.
  • 7 Neurosurgery Department, AP-HP Pitié-Salpêtrière University Hospital, Paris, France.
PMID: 33914067 DOI: 10.1093/neuonc/noab075
Abstract

Background: Malignant meningiomas are fatal and lack effective therapy. As M2 macrophages are the most prevalent immune cell type in human meningiomas, we hypothesized that normalizing this immunosuppressive population would be an effective treatment strategy.

Methods: We used CIBERSORTx to examine the proportions of 22 immune subsets in human meningiomas. We targeted the colony-stimulating factor 1 (CSF1) or CSF1 receptor (CSF1R) axis, an important regulator of macrophage phenotype, using monoclonal antibodies (mAbs) in a novel immunocompetent murine model (MGS1) for malignant meningioma. RNA Sequencing (RNA-seq) was performed to identify changes in gene expression in the tumor microenvironment (TME). Mass cytometry was used to delineate changes in immune subsets after treatment. We measured patients' plasma CSF1 levels using ELISA and CSF1R expression using multiplex quantitative immunofluorescence in a human meningioma tissue microarray.

Results: Human meningiomas are heavily enriched for immunosuppressive myeloid cells. MGS1 recapitulates the TME of human meningiomas, including an abundance of myeloid cells, a paucity of infiltrating T cells, and low programmed death ligand 1 (PD-L1) expression. Treatment of murine meningiomas with anti-CSF1/CSF1R, but not programmed cell death receptor 1 (PD-1), mAbs abrogate tumor growth. RNA-seq and mass cytometry analyses reveal a myeloid cell reprogramming with limited effect on T cells in the TME. CSF1 plasma levels are significantly elevated in human patients, and CSF1R is highly expressed on CD163+ macrophages within the human TME.

Conclusion: Our findings suggest that anti-CSF1/CSF1R antibody treatment may be an effective normalization Cancer Immunotherapy for malignant meningiomas.

Keywords

immunotherapy; macrophage; meningiomas; tumor immunology.

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