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

Author

Listed:
  • Victor Maximov

    (Emory University)

  • Zhihong Chen

    (Emory University
    Emory University)

  • Yun Wei

    (Emory University
    Emory University)

  • M. Hope Robinson

    (Emory University
    Emory University)

  • Cameron J. Herting

    (Emory University
    Emory University)

  • Nithya S. Shanmugam

    (Emory University)

  • Vasilisa A. Rudneva

    (St. Jude Children’s Research Hospital)

  • Kelly C. Goldsmith

    (Emory University
    Emory University)

  • Tobey J. MacDonald

    (Emory University
    Emory University)

  • Paul A. Northcott

    (St. Jude Children’s Research Hospital)

  • Dolores Hambardzumyan

    (Emory University
    Emory University)

  • Anna M. Kenney

    (Emory University
    Emory University)

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.

Suggested Citation

  • 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 Hamb, 2019. "Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10458-9
    DOI: 10.1038/s41467-019-10458-9
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    Cited by:

    1. Zhihong Chen & Nishant Soni & Gonzalo Pinero & Bruno Giotti & Devon J. Eddins & Katherine E. Lindblad & James L. Ross & Montserrat Puigdelloses Vallcorba & Tanvi Joshi & Angelo Angione & Wes Thomason , 2023. "Monocyte depletion enhances neutrophil influx and proneural to mesenchymal transition in glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    2. David R. Ghasemi & Konstantin Okonechnikov & Anne Rademacher & Stephan Tirier & Kendra K. Maass & Hanna Schumacher & Piyush Joshi & Maxwell P. Gold & Julia Sundheimer & Britta Statz & Ahmet S. Rifaiog, 2024. "Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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