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1811091399858192384
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MIT
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© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis1. To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations. We found that the previously described immunoreactive and mesenchymal subtypes of HGSOC, which have prognostic implications, reflect the abundance of immune infiltrates and fibroblasts rather than distinct subsets of malignant cells2. Malignant cell variability was partly explained by heterogeneous copy number alteration patterns or expression of a stemness program. Malignant cells shared expression of inflammatory programs that were largely recapitulated in single-cell RNA sequencing of ~35,000 cells from additionally collected samples, including three ascites, two primary HGSOC tumors and three patient ascites-derived xenograft models. Inhibition of the JAK/STAT pathway, which was expressed in both malignant cells and cancer-associated fibroblasts, had potent anti-tumor activity in primary short-term cultures and patient-derived xenograft models. Our work contributes to resolving the HSGOC landscape3–5 and provides a resource for the development of novel therapeutic approaches.
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2024-09-23T15:01:49Z
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Article
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mit-1721.1/136662
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Massachusetts Institute of Technology
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| language |
English
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2024-09-23T15:01:49Z
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2021
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Springer Science and Business Media LLC
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dspace
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| spelling |
mit-1721.1/1366622021-10-28T03:28:58Z A single-cell landscape of high-grade serous ovarian cancer © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis1. To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations. We found that the previously described immunoreactive and mesenchymal subtypes of HGSOC, which have prognostic implications, reflect the abundance of immune infiltrates and fibroblasts rather than distinct subsets of malignant cells2. Malignant cell variability was partly explained by heterogeneous copy number alteration patterns or expression of a stemness program. Malignant cells shared expression of inflammatory programs that were largely recapitulated in single-cell RNA sequencing of ~35,000 cells from additionally collected samples, including three ascites, two primary HGSOC tumors and three patient ascites-derived xenograft models. Inhibition of the JAK/STAT pathway, which was expressed in both malignant cells and cancer-associated fibroblasts, had potent anti-tumor activity in primary short-term cultures and patient-derived xenograft models. Our work contributes to resolving the HSGOC landscape3–5 and provides a resource for the development of novel therapeutic approaches. 2021-10-27T20:36:31Z 2021-10-27T20:36:31Z 2020 2021-07-22T15:13:35Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136662 en 10.1038/S41591-020-0926-0 Nature Medicine Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC PMC
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| spellingShingle |
A single-cell landscape of high-grade serous ovarian cancer
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| title |
A single-cell landscape of high-grade serous ovarian cancer
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| title_full |
A single-cell landscape of high-grade serous ovarian cancer
|
| title_fullStr |
A single-cell landscape of high-grade serous ovarian cancer
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| title_full_unstemmed |
A single-cell landscape of high-grade serous ovarian cancer
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| title_short |
A single-cell landscape of high-grade serous ovarian cancer
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| title_sort |
single cell landscape of high grade serous ovarian cancer
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| url |
https://hdl.handle.net/1721.1/136662
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