Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma
| Autor: | Dolores Hambardzumyan, Kelly C. Goldsmith, M. Hope Robinson, Victor Maximov, Vasilisa A. Rudneva, Zhihong Chen, Anna Kenney, Paul A. Northcott, Cameron Herting, Nithya S. Shanmugam, Tobey J. MacDonald, Yun Wei |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy 02 engineering and technology Mice Tumor Microenvironment Medicine Macrophage Myeloid Cells Sonic hedgehog Receptor skin and connective tissue diseases lcsh:Science Chemokine CCL2 Multidisciplinary CD11b Antigen biology Microfilament Proteins 021001 nanoscience & nanotechnology 3. Good health Up-Regulation DNA-Binding Proteins Tumour immunology Microglia 0210 nano-technology hormones hormone substitutes and hormone antagonists Receptors CCR2 Science Antigens Differentiation Myelomonocytic General Biochemistry Genetics and Molecular Biology Article Paediatric cancer 03 medical and health sciences Downregulation and upregulation stomatognathic system In vivo Antigens CD Animals Humans Hedgehog Proteins Cerebellar Neoplasms Survival rate neoplasms Medulloblastoma business.industry Macrophages Calcium-Binding Proteins General Chemistry medicine.disease nervous system diseases CNS cancer Disease Models Animal 030104 developmental biology biology.protein Cancer research lcsh:Q business Ex vivo |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-11 (2019) |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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