Athymic mice reveal a requirement for T-cell-microglia interactions in establishing a microenvironment supportive of Nf1 low-grade glioma growth

Genes Dev. 2018 Apr 1;32(7-8):491-496. doi: 10.1101/gad.310797.117. Epub 2018 Apr 9.

Abstract

Pediatric low-grade gliomas (LGGs) frequently do not engraft in immunocompromised mice, limiting their use as an experimental platform. In contrast, murine Neurofibromatosis-1 (Nf1) optic LGG stem cells (o-GSCs) form glioma-like lesions in wild-type, but not athymic, mice following transplantation. Here, we show that the inability of athymic mice to support o-GSC engraftment results from impaired microglia/macrophage function, including reduced expression of Ccr2 and Ccl5, both of which are required for o-GSC engraftment and Nf1 optic glioma growth. Impaired Ccr2 and Ccl5 expression in athymic microglia/macrophages was restored by T-cell exposure, establishing T-cell-microglia/macrophage interactions as critical stromal determinants that support NF1 LGG growth.

Keywords: chemokines; monocyte; stroma; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokine CCL5 / biosynthesis
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / physiology
  • Gene Expression
  • Genes, Neurofibromatosis 1
  • Glioma / genetics
  • Glioma / immunology*
  • Glioma / metabolism
  • Glioma / pathology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Microglia / immunology*
  • Microglia / metabolism
  • Microglia / pathology
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / immunology*

Substances

  • Ccl5 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL5
  • Receptors, CCR2