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

Nat Commun. 2019 Jun 3;10(1):2410. doi: 10.1038/s41467-019-10458-9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • CD11b Antigen / genetics
  • CD11b Antigen / metabolism
  • Calcium-Binding Proteins
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / immunology*
  • Cerebellar Neoplasms / metabolism
  • Chemokine CCL2 / immunology
  • Chemokine CCL2 / metabolism
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Hedgehog Proteins / metabolism
  • Humans
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Medulloblastoma / genetics
  • Medulloblastoma / immunology*
  • Medulloblastoma / metabolism
  • Mice
  • Microfilament Proteins
  • Microglia / immunology
  • Myeloid Cells / immunology
  • Receptors, CCR2 / genetics
  • Tumor Microenvironment / immunology*
  • Up-Regulation

Substances

  • AIF1 protein, human
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD11b Antigen
  • CD68 antigen, human
  • Calcium-Binding Proteins
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • DNA-Binding Proteins
  • Hedgehog Proteins
  • ITGAM protein, human
  • Microfilament Proteins
  • Receptors, CCR2