Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages
NKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and hu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32919 |
| _version_ | 1828167325354819584 |
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| author | Thornton W Thompson Benjamin T Jackson P Jonathan Li Jiaxi Wang Alexander Byungsuk Kim Kristen Ting Hui Huang Lily Zhang David H Raulet |
| author_facet | Thornton W Thompson Benjamin T Jackson P Jonathan Li Jiaxi Wang Alexander Byungsuk Kim Kristen Ting Hui Huang Lily Zhang David H Raulet |
| author_sort | Thornton W Thompson |
| collection | DOAJ |
| description | NKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and humans. Here we show that in transplanted tumors and genetically engineered mouse cancer models, tumor-associated macrophages are induced to express the NKG2D ligand RAE-1δ. We find that a soluble factor produced by tumor cells is responsible for macrophage RAE-1δ induction, and we identify tumor-derived colony-stimulating factor-1 (CSF-1) as necessary and sufficient for macrophage RAE-1δ induction in vitro and in vivo. Furthermore, we show that induction of RAE-1δ on macrophages by CSF-1 requires PI3K p110α kinase signaling. Thus, production of CSF-1 by tumor cells leading to activation of PI3K p110α represents a novel cellular and molecular pathway mediating NKG2D ligand expression on tumor-associated macrophages. |
| first_indexed | 2024-04-12T02:15:52Z |
| format | Article |
| id | doaj.art-a0150a9442354866b4ce50e5b63a7e36 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:15:52Z |
| publishDate | 2018-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a0150a9442354866b4ce50e5b63a7e362022-12-22T03:52:15ZengeLife Sciences Publications LtdeLife2050-084X2018-05-01710.7554/eLife.32919Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophagesThornton W Thompson0https://orcid.org/0000-0002-6352-8238Benjamin T Jackson1P Jonathan Li2Jiaxi Wang3Alexander Byungsuk Kim4https://orcid.org/0000-0002-6425-4566Kristen Ting Hui Huang5Lily Zhang6David H Raulet7https://orcid.org/0000-0002-1257-8649Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesNKG2D is an important immunoreceptor expressed on the surface of NK cells and some T cells. NKG2D recognizes a set of ligands typically expressed on infected or transformed cells, but recent studies have also documented NKG2D ligands on subsets of host non-tumor cells in tumor-bearing animals and humans. Here we show that in transplanted tumors and genetically engineered mouse cancer models, tumor-associated macrophages are induced to express the NKG2D ligand RAE-1δ. We find that a soluble factor produced by tumor cells is responsible for macrophage RAE-1δ induction, and we identify tumor-derived colony-stimulating factor-1 (CSF-1) as necessary and sufficient for macrophage RAE-1δ induction in vitro and in vivo. Furthermore, we show that induction of RAE-1δ on macrophages by CSF-1 requires PI3K p110α kinase signaling. Thus, production of CSF-1 by tumor cells leading to activation of PI3K p110α represents a novel cellular and molecular pathway mediating NKG2D ligand expression on tumor-associated macrophages.https://elifesciences.org/articles/32919NKG2DmacrophageCSF-1tumor microenvironment |
| spellingShingle | Thornton W Thompson Benjamin T Jackson P Jonathan Li Jiaxi Wang Alexander Byungsuk Kim Kristen Ting Hui Huang Lily Zhang David H Raulet Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages eLife NKG2D macrophage CSF-1 tumor microenvironment |
| title | Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages |
| title_full | Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages |
| title_fullStr | Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages |
| title_full_unstemmed | Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages |
| title_short | Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages |
| title_sort | tumor derived csf 1 induces the nkg2d ligand rae 1δ on tumor infiltrating macrophages |
| topic | NKG2D macrophage CSF-1 tumor microenvironment |
| url | https://elifesciences.org/articles/32919 |
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