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

Victor Maximov, Zhihong Chen, Yun Wei, M. Hope Robinson, Cameron J. Herting, Nithya S. Shanmugam, Vasilisa A. Rudneva, Kelly C. Goldsmith, Tobey J. MacDonald, Paul A. Northcott, Dolores Hambardzumyan and Anna M. Kenney ()
Additional contact information
Victor Maximov: Emory University
Zhihong Chen: Emory University
Yun Wei: Emory University
M. Hope Robinson: Emory University
Cameron J. Herting: Emory University
Nithya S. Shanmugam: Emory University
Vasilisa A. Rudneva: St. Jude Children’s Research Hospital
Kelly C. Goldsmith: Emory University
Tobey J. MacDonald: Emory University
Paul A. Northcott: St. Jude Children’s Research Hospital
Dolores Hambardzumyan: Emory University
Anna M. Kenney: Emory University

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10458-9

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