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

Yuan Pan, Min Xiong, Ran Chen, Yu Ma, Courtney Corman, Meron Maricos, Urs Kindler, Marcus Semtner, Yi Hsien Chen, Sonika Dahiya, David H. Gutmann

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)491-496
Number of pages6
JournalGenes and Development
Volume32
Issue number7-8
DOIs
StatePublished - Apr 1 2018

Keywords

  • Chemokines
  • Monocyte
  • Stroma
  • Tumor microenvironment

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