title: The immune cell infiltrate populating meningiomas is composed of mature, antigen-experienced T and B cells.
abstract: BACKGROUND
  Meningiomas often harbor an immune cell infiltrate that can include substantial numbers of T and B cells. However, their phenotype and characteristics remain undefined. To gain a deeper understanding of the T and B cell repertoire in this tumor, we characterized the immune infiltrate of 28 resected meningiomas representing all grades.
  
  
  METHODS
  Immunohistochemistry was used to grossly characterize and enumerate infiltrating lymphocytes. A molecular analysis of the immunoglobulin variable region of tumor-infiltrating B cells was used to characterize their antigen experience. Flow cytometry of fresh tissue homogenate and paired peripheral blood lymphocytes was used to identify T cell phenotypes and characterize the T cell repertoire.
  
  
  RESULTS
  A conspicuous B and T cell infiltrate, primarily clustered in perivascular spaces, was present in the microenvironment of most tumors examined. Characterization of 294 tumor-infiltrating B cells revealed clear evidence of antigen experience, in that the cardinal features of an antigen-driven B cell response were present. Meningiomas harbored populations of antigen-experienced CD4+ and CD8+ memory/effector T cells, regulatory T cells, and T cells expressing the immune checkpoint molecules PD-1 and Tim-3, indicative of exhaustion. All of these phenotypes were considerably enriched relative to their frequency in the circulation. The T cell repertoire in the tumor microenvironment included populations that were not reflected in paired peripheral blood.
  
  
  CONCLUSIONS
  The tumor microenvironment of meningiomas often includes postgerminal center B cell populations. These tumors invariably include a selected, antigen-experienced, effector T cell population enriched by those that express markers of an exhausted phenotype.
authors: Corresponding Author: Dr. Kevin C. O'Connor, PhD, Yale School of Medicine, 300 George Street, Room 353J, New Haven, CT, USA 06511.. kevin.oconnor@yale.edu.
authors: Liangjuan
authors: L
authors: Fang
authors: Daniel E
authors: DE
authors: Lowther
authors: Matthew L
authors: ML
authors: Meizlish
authors: Richard C E
authors: RC
authors: Anderson
authors: Jeffrey N
authors: JN
authors: Bruce
authors: Lesley
authors: L
authors: Devine
authors: Anita J
authors: AJ
authors: Huttner
authors: Steven H
authors: SH
authors: Kleinstein
authors: Jae-Yun
authors: JY
authors: Lee
authors: Joel N H
authors: JN
authors: Stern
authors: Gur
authors: G
authors: Yaari
authors: Laura
authors: L
authors: Lovato
authors: Katharine M
authors: KM
authors: Cronk
authors: Kevin C
authors: KC
authors: O'Connor
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060966:Clonal Selection, Antigen-Mediated; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008577:Meningeal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
keywords: B cell; T cell; meningioma; tumor-infiltrating lymphocytes
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