Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546707/
https://www.ncbi.nlm.nih.gov/pubmed/31160587
http://dx.doi.org/10.1038/s41467-019-10458-9
_version_ 1783423558901301248
author 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.
author_facet 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.
author_sort Maximov, Victor
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6546707
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-65467072019-06-18 Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma 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. Nat Commun Article 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. Nature Publishing Group UK 2019-06-03 /pmc/articles/PMC6546707/ /pubmed/31160587 http://dx.doi.org/10.1038/s41467-019-10458-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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.
Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
title Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
title_full Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
title_fullStr Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
title_full_unstemmed Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
title_short Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
title_sort tumour-associated macrophages exhibit anti-tumoural properties in sonic hedgehog medulloblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546707/
https://www.ncbi.nlm.nih.gov/pubmed/31160587
http://dx.doi.org/10.1038/s41467-019-10458-9
work_keys_str_mv AT maximovvictor tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT chenzhihong tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT weiyun tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT robinsonmhope tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT hertingcameronj tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT shanmugamnithyas tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT rudnevavasilisaa tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT goldsmithkellyc tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT macdonaldtobeyj tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT northcottpaula tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT hambardzumyandolores tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma
AT kenneyannam tumourassociatedmacrophagesexhibitantitumouralpropertiesinsonichedgehogmedulloblastoma