About this item:

121 Views | 100 Downloads

Author Notes:

Correspondence to: Dolores Hambardzumyan, PhD, 1760 Haygood Drive, E-380, Atlanta, 30329, GA, USA, dhambar@emory.edu.

The authors are grateful to Dr. Christopher Nelson for editorial assistance.

We thank the Flow Cytometry Cores at the CCF and the CHOA for technical services.

We acknowledge the excellent imaging assistance from Dr. Neil Anthony.

We thank Ms. Jennifer Powers for cell sorting.

We are grateful to the Biostatistics and Bioinformatics services at Washington University and Emory University.

The authors thank Dr. Richard Ransohoff for providing the Cx3cr1GFP/WT;Ccr2RFP/WT mice and Dr. Helmut Kettenmann for providing GL261 tumor samples.

The authors declare no Conflict of Interests.

Subjects:

Research Funding:

This work was supported by NCI grants U01CA160882 (to D. Hambardzumyan and D.H. Gutmann) and R01CA195692 (to D.H. Gutmann).

This research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core of the Emory+Children’s Pediatric Research Center.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • FRACTALKINE RECEPTOR
  • RESIDENT MICROGLIA
  • ADULT BRAIN
  • INFILTRATING MONOCYTES
  • GROWTH
  • CNS
  • PROGRESSION
  • RECRUITMENT
  • REVEALS
  • GLIOMAS

Cellular and Molecular Identity of Tumor-Associated Macrophages in Glioblastoma

Show all authors Show less authors

Tools:

Journal Title:

Cancer Research

Volume:

Volume 77, Number 9

Publisher:

, Pages 2266-2278

Type of Work:

Article | Post-print: After Peer Review

Abstract:

In glioblastoma (GBM), tumor-associated macrophages (TAM) represent up to one half of the cells of the tumor mass, including both infiltrating macrophages and resident brain microglia. In an effort to delineate the temporal and spatial dynamics of TAM composition during gliomagenesis, we used genetically engineered and GL261-induced mouse models in combination with CX3CR1 GFP/WT ; CCR2 RFP/WT double knock-in mice. Using this approach, we demonstrated that CX3CR1 Lo CCR2 Hi monocytes were recruited to theGBM,where they transitioned to CX3CR1 Hi CCR2 Lo macrophages and CX3CR1 Hi CCR2 - microglia-like cells. Infiltrating macrophages/ monocytes constituted approximately 85% of the total TAM population, with resident microglia accounting for the approximately 15% remaining. Bone marrow-derived infiltrating macrophages/ monocytes were recruited to the tumor early during GBM initiation, where they localized preferentially to perivascular areas. In contrast, resident microglia were localized mainly to peritumoral regions. RNA-sequencing analyses revealed differential gene expression patterns unique to infiltrating and resident cells, suggesting unique functions for each TAM population. Notably, limiting monocyte infiltration via genetic Ccl2 reduction prolonged the survival of tumor-bearing mice. Our findings illuminate the unique composition and functions of infiltrating and resident myeloid cells in GBM, establishing a rationale to target infiltrating cells in this neoplasm.

Copyright information:

© 2017 American Association for Cancer Research.

Export to EndNote