CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic Hedgehog-Medulloblastoma model

Oncogene. 2021 Jan;40(2):396-407. doi: 10.1038/s41388-020-01536-0. Epub 2020 Nov 6.


The immune microenvironment of tumors can play a critical role in promoting or inhibiting tumor progression depending on the context. We present evidence that tumor-associated macrophages/microglia (TAMs) can promote tumor progression in the sonic hedgehog subgroup of medulloblastoma (SHH-MB). By combining longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) and immune profiling of a sporadic mouse model of SHH-MB, we found the density of TAMs is higher in the ~50% of tumors that progress to lethal disease. Furthermore, reducing regulatory T cells or eliminating B and T cells in Rag1 mutants does not alter SHH-MB tumor progression. As TAMs are a dominant immune component in tumors and are normally dependent on colony-stimulating factor 1 receptor (CSF1R), we treated mice with a CSF1R inhibitor, PLX5622. Significantly, PLX5622 reduces a subset of TAMs, prolongs mouse survival, and reduces the volume of most tumors within 4 weeks of treatment. Moreover, concomitant with a reduction in TAMs the percentage of infiltrating cytotoxic T cells is increased, indicating a change in the tumor environment. Our studies in an immunocompetent preclinical mouse model demonstrate TAMs can have a functional role in promoting SHH-MB progression. Thus, CSF1R inhibition could have therapeutic potential for a subset of SHH-MB patients.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Cell Proliferation
  • Cerebellar Neoplasms / etiology
  • Cerebellar Neoplasms / metabolism
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / prevention & control*
  • Disease Models, Animal*
  • Female
  • Hedgehog Proteins / physiology*
  • Humans
  • Male
  • Medulloblastoma / etiology
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology
  • Medulloblastoma / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Prognosis
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Tumor Cells, Cultured
  • Tumor Microenvironment
  • Tumor-Associated Macrophages / immunology*


  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Csf1r protein, mouse
  • Hedgehog Proteins
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor