Association between inflammatory infiltrates and isolated monosomy 22/del(22q) in meningiomas

PLoS One. 2013 Oct 1;8(10):e74798. doi: 10.1371/journal.pone.0074798. eCollection 2013.

Abstract

Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69(+) lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69(+), CD63(+), CD16(+) and CD33(+) cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen-Presenting Cells / immunology
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 22 / genetics*
  • Female
  • Humans
  • Inflammation / immunology
  • Karyotype
  • Lymphocytes / immunology
  • Male
  • Meningeal Neoplasms / genetics*
  • Meningeal Neoplasms / immunology*
  • Meningioma / genetics*
  • Meningioma / immunology*
  • Middle Aged
  • Transcriptome
  • Young Adult

Grants and funding

This work was partially supported by grants from the Fundação para a Ciência e Tecnologia (PIC/IC/83108/2007, FCT, Portugal), Fondo de Investigaciones Sanitarias (FIS/FEDER 06/0312 and RETICC RD06/0020/0035, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain), Caja Burgos (Spain), and Fundación MMA (exp 75312010 and 87692011, Madrid, Spain). Patrícia Domingues is supported by grant (SFRH/BD/64799/2009) from FCT. Maria Dolores Tabernero is supported by IECSCYL (Soria, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.