The tumour microenvironment creates a niche for the self-renewal of tumour-promoting macrophages in colon adenoma

Nat Commun. 2018 Feb 8;9(1):582. doi: 10.1038/s41467-018-02834-8.


Circulating CCR2+ monocytes are crucial for maintaining the adult tissue-resident F4/80hiMHCIIhi macrophage pool in the intestinal lamina propria. Here we show that a subpopulation of CCR2-independent F4/80hiMHCIIlow macrophages, which are the most abundant F4/80hi cells in neonates, gradually decline in number in adulthood; these macrophages likely represent the fetal contribution to F4/80hi cells. In colon adenomas of ApcMin/+ mice, F4/80hiMHCIIlow macrophages are not only preserved, but become the dominant subpopulation among tumour-resident macrophages during tumour progression. Furthermore, these pro-tumoural F4/80hiMHCIIlow and F4/80hiMHCIIhi macrophages can self-renew in the tumour and maintain their numbers mostly independent from bone marrow contribution. Analyses of colon adenomas indicate that CSF1 may be a key facilitator of macrophage self-renewal. In summary, the tumour microenvironment creates an isolated niche for tissue-resident macrophages that favours macrophage survival and self-renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / immunology*
  • Adenomatous Polyposis Coli Protein / genetics
  • Animals
  • Antigens, Differentiation
  • Cell Self Renewal*
  • Cell Survival
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology*
  • Colonic Polyps / genetics
  • Colonic Polyps / immunology*
  • Histocompatibility Antigens Class II
  • Macrophage Colony-Stimulating Factor
  • Macrophages / cytology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasms, Experimental
  • Receptors, CCR2 / genetics
  • Stem Cell Niche*
  • Tumor Microenvironment*


  • Adenomatous Polyposis Coli Protein
  • Antigens, Differentiation
  • Ccr2 protein, mouse
  • Histocompatibility Antigens Class II
  • Receptors, CCR2
  • adenomatous polyposis coli protein, mouse
  • monocyte-macrophage differentiation antigen
  • Macrophage Colony-Stimulating Factor