The immune cell infiltrate populating meningiomas is composed of mature, antigen-experienced T and B cells

Liangjuan Fang, Daniel E. Lowther, Matthew L. Meizlish, Richard C.E. Anderson, Jeffrey N. Bruce, Lesley Devine, Anita J. Huttner, Steven H. Kleinstein, Jae Yun Lee, Joel N.H. Stern, Gur Yaari, Laura Lovato, Katharine M. Cronk, Kevin C. O'Connor

Research output: Contribution to journalArticlepeer-review


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 lymphocyteswasused to identifyTcell phenotypesandcharacterize 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 phenotypeswere considerably enriched relative to their frequency in the circulation. The T cell repertoire in the tumor microenvironmentincludedpopulationsthatwerenot reflected in paired peripheral blood. Conclusion. 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.

Original languageEnglish
Pages (from-to)1479-1490
Number of pages12
Issue number11
StatePublished - 1 Nov 2013
Externally publishedYes


  • B cell
  • Meningioma
  • T cell
  • Tumor-infiltrating lymphocytes

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Oncology
  • Cancer Research


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