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dc.contributor.authorSoncin, Ireneen
dc.identifier.citationSoncin, I. (2018). Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation. Doctoral thesis, Nanyang Technological University, Singapore.en
dc.description.abstractMacrophages 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.en
dc.format.extent164 p.en
dc.subjectDRNTU::Science::Biological sciencesen
dc.titleOntogeny of intestinal intratumoural macrophages and their contribution in cancer regulationen
dc.contributor.supervisorRuedl Christianeen
dc.contributor.schoolSchool of Biological Sciencesen
dc.description.degreeDoctor of Philosophyen
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