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Author Notes:

A.M.K. (email: anna.kenney@emory.edu)

V.M., D.H. and A.M.K. contributed to conception, design of the study and methodology; V.M., Z.C., C.J.H., Y.W., N.S.S. and M.H.R. acquired, analysed and interpreted the data; V.M., V.A.R. and P.A.N. analysed the human patient data; V.M., Z.C., D.H. and A.M.K. wrote the paper; K.C.G. and T.J.M. provided additional material support and comments; All authors read the manuscript and approved the final version.

We thank the Pathology Core Laboratory of Winship Cancer Institute for paraffin embedding of tissues and whole-slide scanning; Children’s Healthcare of Atlanta and Emory Pediatrics Flow Cytometry Core for help with flow cytometry; as well as Neil Anthony and Emory Integrated Cellular Imaging Core for help with images acquisition and analysis.

We thank Dmitry Shayakhmetov and Nelson Di Paolo for help with BMDM cultures and productive discussions.

We would like to thank Robert Wechsler-Reya and Alexandra Garancher for providing MB group 3 mouse model cells.

The authors declare no competing interests.

Subjects:

Research Funding:

This work was supported by: R01-NS061070 (A.M.K.); U01-CA160882 (D.H.); R01-NS100864 (D.H.); NCI Winship Cancer Institute P30 Centre Grant CA138292; 1F31NS106887 (C.J.H.); Sontag Foundation (P.A.N.); V Foundation (P.A.N.) and American Lebanese Syrian Associated Charities (P.A.N.).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • NERVOUS-SYSTEM
  • MODEL
  • INHIBITION
  • EXPRESSION
  • MICROGLIA
  • MONOCYTES
  • SUBGROUP
  • GROWTH

Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma

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Journal Title:

Nature Communications

Volume:

Volume 10, Number 1

Publisher:

, Pages 2410-2410

Type of Work:

Article | Final Publisher PDF

Abstract:

Medulloblastoma, which is the most common malignant paediatric brain tumour, has a 70% survival rate, but standard treatments often lead to devastating life-long side effects and recurrence is fatal. One of the emerging strategies in the search for treatments is to determine the roles of tumour microenvironment cells in the growth and maintenance of tumours. The most attractive target is tumour-associated macrophages (TAMs), which are abundantly present in the Sonic Hedgehog (SHH) subgroup of medulloblastoma. Here, we report an unexpected beneficial role of TAMs in SHH medulloblastoma. In human patients, decreased macrophage number is correlated with significantly poorer outcome. We confirm macrophage anti-tumoural behaviour in both ex vivo and in vivo murine models of SHH medulloblastoma. Taken together, our findings suggest that macrophages play a positive role by impairing tumour growth in medulloblastoma, in contrast to the pro-tumoural role played by TAMs in glioblastoma, another common brain tumour.

Copyright information:

© 2019, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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