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

• Type of Material: Article
• Authors: 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 MacDonald, Emory University; Paul A. Northcott, St. Jude Children’s Research Hospital; Dolares Hambardzumyan, Emory University; Marye McKenney, Emory University
• Language: English
• Date: 2019-06-03
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-019-10458-9
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 10
• Issue: 1
• Start Page: 2410
• End Page: 2410
• Grant/Funding Information: 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 - Other Topics; SUBGROUP; MODEL; GROWTH; MONOCYTES; NERVOUS-SYSTEM; Science & Technology; EXPRESSION; MICROGLIA; INHIBITION; Multidisciplinary Sciences
• Research Categories: Biology, Neuroscience; Health Sciences, Oncology

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.