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


ABSTRACT: 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.

SUBMITTER: Soncin I 

PROVIDER: S-EPMC5805689 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Soncin Irene I   Sheng Jianpeng J   Chen Qi Q   Foo Shihui S   Duan Kaibo K   Lum Josephine J   Poidinger Michael M   Zolezzi Francesca F   Karjalainen Klaus K   Ruedl Christiane C  

Nature communications 20180208 1


Circulating CCR2<sup>+</sup> monocytes are crucial for maintaining the adult tissue-resident F4/80<sup>hi</sup>MHCII<sup>hi</sup> macrophage pool in the intestinal lamina propria. Here we show that a subpopulation of CCR2-independent F4/80<sup>hi</sup>MHCII<sup>low</sup> macrophages, which are the most abundant F4/80<sup>hi</sup> cells in neonates, gradually decline in number in adulthood; these macrophages likely represent the fetal contribution to F4/80<sup>hi</sup> cells. In colon adenomas of  ...[more]

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