Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment
Abstract Cancer metastasis to the brain is a significant clinical problem. Metastasis is the consequence of favorable interactions between invaded cancer cells and the microenvironment. Here, we demonstrate that cancer-activated astrocytes create a sustained low-level activated type I interferon (IF...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38252-8 |
| _version_ | 1797832047416311808 |
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| author | Weili Ma Maria Cecília Oliveira-Nunes Ke Xu Andrew Kossenkov Benjamin C. Reiner Richard C. Crist James Hayden Qing Chen |
| author_facet | Weili Ma Maria Cecília Oliveira-Nunes Ke Xu Andrew Kossenkov Benjamin C. Reiner Richard C. Crist James Hayden Qing Chen |
| author_sort | Weili Ma |
| collection | DOAJ |
| description | Abstract Cancer metastasis to the brain is a significant clinical problem. Metastasis is the consequence of favorable interactions between invaded cancer cells and the microenvironment. Here, we demonstrate that cancer-activated astrocytes create a sustained low-level activated type I interferon (IFN) microenvironment in brain metastatic lesions. We further confirm that the IFN response in astrocytes facilitates brain metastasis. Mechanistically, IFN signaling in astrocytes activates C-C Motif Chemokine Ligand 2 (CCL2) production, which further increases the recruitment of monocytic myeloid cells. The correlation between CCL2 and monocytic myeloid cells is confirmed in clinical brain metastasis samples. Lastly, genetically or pharmacologically inhibiting C-C Motif Chemokine Receptor 2 (CCR2) reduces brain metastases. Our study clarifies a pro-metastatic effect of type I IFN in the brain even though IFN response has been considered to have anti-tumor effects. Moreover, this work expands our understandings on the interactions between cancer-activated astrocytes and immune cells in brain metastasis. |
| first_indexed | 2024-04-09T14:01:29Z |
| format | Article |
| id | doaj.art-c50d61d0f5a74a329e60705f1e43cf8e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T14:01:29Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c50d61d0f5a74a329e60705f1e43cf8e2023-05-07T11:18:13ZengNature PortfolioNature Communications2041-17232023-05-0114111810.1038/s41467-023-38252-8Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitmentWeili Ma0Maria Cecília Oliveira-Nunes1Ke Xu2Andrew Kossenkov3Benjamin C. Reiner4Richard C. Crist5James Hayden6Qing Chen7Immunology, Microenvironment and Metastasis Program, The Wistar InstituteImmunology, Microenvironment and Metastasis Program, The Wistar InstituteMD/PhD Program, Boston University School of MedicineGene Expression & Regulation Program, The Wistar InstituteDepartment of Psychiatry, Perelman School of Medicine, The University of PennsylvaniaDepartment of Psychiatry, Perelman School of Medicine, The University of PennsylvaniaImaging Shared Resource, The Wistar InstituteImmunology, Microenvironment and Metastasis Program, The Wistar InstituteAbstract Cancer metastasis to the brain is a significant clinical problem. Metastasis is the consequence of favorable interactions between invaded cancer cells and the microenvironment. Here, we demonstrate that cancer-activated astrocytes create a sustained low-level activated type I interferon (IFN) microenvironment in brain metastatic lesions. We further confirm that the IFN response in astrocytes facilitates brain metastasis. Mechanistically, IFN signaling in astrocytes activates C-C Motif Chemokine Ligand 2 (CCL2) production, which further increases the recruitment of monocytic myeloid cells. The correlation between CCL2 and monocytic myeloid cells is confirmed in clinical brain metastasis samples. Lastly, genetically or pharmacologically inhibiting C-C Motif Chemokine Receptor 2 (CCR2) reduces brain metastases. Our study clarifies a pro-metastatic effect of type I IFN in the brain even though IFN response has been considered to have anti-tumor effects. Moreover, this work expands our understandings on the interactions between cancer-activated astrocytes and immune cells in brain metastasis.https://doi.org/10.1038/s41467-023-38252-8 |
| spellingShingle | Weili Ma Maria Cecília Oliveira-Nunes Ke Xu Andrew Kossenkov Benjamin C. Reiner Richard C. Crist James Hayden Qing Chen Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment Nature Communications |
| title | Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment |
| title_full | Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment |
| title_fullStr | Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment |
| title_full_unstemmed | Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment |
| title_short | Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment |
| title_sort | type i interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment |
| url | https://doi.org/10.1038/s41467-023-38252-8 |
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