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

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 micr...

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Veröffentlicht in:Nature communications 2019-06, Vol.10 (1), p.2410-2410, Article 2410
Hauptverfasser: Maximov, Victor, Chen, Zhihong, Wei, Yun, Robinson, M. Hope, Herting, Cameron J., Shanmugam, Nithya S., Rudneva, Vasilisa A., Goldsmith, Kelly C., MacDonald, Tobey J., Northcott, Paul A., Hambardzumyan, Dolores, Kenney, Anna M.
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Sprache:eng
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Zusammenfassung: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. The Sonic Hedgehog subgroup of medulloblastoma are characterised by the high infiltration of tumour-associated macrophages (TAMs). Here, the authors show that TAM numbers in patients are associated with better prognosis and that, consistently, in a murine model of medulloblastoma, these TAMs have anti-tumoural properties.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-10458-9