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|Title:||Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation||Authors:||Soncin, Irene||Keywords:||DRNTU::Science::Biological sciences||Issue Date:||2018||Source:||Soncin, I. (2018). Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation. Doctoral thesis, Nanyang Technological University, Singapore.||Abstract:||Macrophages are tissue-resident myeloid cells that can contribute to the initiation and progression of cancer. A better understanding of their ontogeny and survival mechanisms is crucial for the development of effective macrophage-based immunotherapies. In colorectal cancer, these aspects have not been investigated thus far. In this work, in addition to confirming the monocyte-dependence of F4/80(hi)MHCII(hi) macrophages in colon lamina propria (LP), we have identified a previously overlooked CCR2-independent F4/80(hi)MHCII(lo) macrophage subset, which declines after birth and is almost entirely outcompeted by CCR2-dependent F4/80(hi)MHCII(hi) macrophages. Interestingly, in colon adenomas F4/80(hi)MHCII(lo) cells become the dominant macrophage fraction during tumour progression. In contrast to their LP counterparts, the intratumoural F4/80(hi) macrophages are able to self-renew and lose the bone marrow dependency. Since their depletion via CSF1R blockade diminishes the tumour burden, our data underline the potential of these tumour-promoting intestinal macrophages as an attractive target for successful cancer immunotherapies.||URI:||https://hdl.handle.net/10356/88034
|DOI:||10.32657/10220/46940||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Theses|
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