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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| Format: | Thesis |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/88034 http://hdl.handle.net/10220/46940 |
| _version_ | 1824455852393758720 |
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| author | Soncin, Irene |
| author2 | Ruedl Christiane |
| author_facet | Ruedl Christiane Soncin, Irene |
| author_sort | Soncin, Irene |
| collection | NTU |
| 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. |
| first_indexed | 2025-02-19T03:44:47Z |
| format | Thesis |
| id | ntu-10356/88034 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:44:47Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-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 |
| spellingShingle | DRNTU::Science::Biological sciences Soncin, Irene Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
| title | 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_short | Ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
| title_sort | ontogeny of intestinal intratumoural macrophages and their contribution in cancer regulation |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/88034 http://hdl.handle.net/10220/46940 |
| work_keys_str_mv | AT soncinirene ontogenyofintestinalintratumouralmacrophagesandtheircontributionincancerregulation |