Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation
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 b...
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sg-ntu-dr.10356-880342023-02-28T18:50:39Z Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation Soncin, Irene Ruedl Christiane School of Biological Sciences DRNTU::Science::Biological sciences 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. Doctor of Philosophy 2018-12-12T14:05:12Z 2019-12-06T16:54:35Z 2018-12-12T14:05:12Z 2019-12-06T16:54:35Z 2018 Thesis Soncin, I. (2018). Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/88034 http://hdl.handle.net/10220/46940 10.32657/10220/46940 en 164 p. application/pdf |
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DRNTU::Science::Biological sciences Soncin, Irene Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
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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. |
author2 |
Ruedl Christiane |
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Ruedl Christiane Soncin, Irene |
format |
Theses and Dissertations |
author |
Soncin, Irene |
author_sort |
Soncin, Irene |
title |
Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
title_short |
Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
title_full |
Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
title_fullStr |
Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
title_full_unstemmed |
Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
title_sort |
ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/88034 http://hdl.handle.net/10220/46940 |
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1759858152056029184 |