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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Main Author: Soncin, Irene
Other Authors: Ruedl Christiane
Format: Theses and Dissertations
Language:English
Published: 2018
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Online Access:https://hdl.handle.net/10356/88034
http://hdl.handle.net/10220/46940
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Institution: Nanyang Technological University
Language: English
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spelling 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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Soncin, Irene
Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation
description 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
author_facet 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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