title: Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma.
abstract: There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma - both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Malak
authors.initials: M
authors.lastname: Abedalthagafi
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ayal A
authors.initials: AA
authors.lastname: Aizer
authors.affiliation: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: McHenry
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Sun
authors.affiliation: Imaging Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Mark-Anthony
authors.initials: MA
authors.lastname: Bray
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Viramontes
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Revaz
authors.initials: R
authors.lastname: Machaidze
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Department of Neuro-Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Priscilla K
authors.initials: PK
authors.lastname: Brastianos
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Dunn
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Imaging Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Carpenter
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Alexander
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Nathalie Y
authors.initials: NY
authors.lastname: Agar
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.affiliation: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Bradshaw
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sandro
authors.initials: S
authors.lastname: Santagata
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008577:Meningeal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008579:Meningioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D012333:RNA, Messenger
keywords: PD-L1; RNAscope; immunotherapy; meningioma