Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125
<jats:title>Abstract</jats:title> <jats:p>Malignant ascites is a common clinical problem in ovarian cancer. NK cells are present in the ascites, but their antitumor activity is inhibited. The underlying mechanisms of the inhibition have yet to be fully elucidated. U...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The American Association of Immunologists
2023
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| Online Access: | https://hdl.handle.net/1721.1/147988 |
| _version_ | 1826200566458482688 |
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| author | Fraser, Christopher C Jia, Bin Hu, Guangan Al Johani, Lojain Ibrahim Fritz-Klaus, Roberta Ham, James Dongjoo Fichorova, Raina N Elias, Kevin M Cramer, Daniel William Patankar, Manish S Chen, Jianzhu |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Fraser, Christopher C Jia, Bin Hu, Guangan Al Johani, Lojain Ibrahim Fritz-Klaus, Roberta Ham, James Dongjoo Fichorova, Raina N Elias, Kevin M Cramer, Daniel William Patankar, Manish S Chen, Jianzhu |
| author_sort | Fraser, Christopher C |
| collection | MIT |
| description | <jats:title>Abstract</jats:title>
<jats:p>Malignant ascites is a common clinical problem in ovarian cancer. NK cells are present in the ascites, but their antitumor activity is inhibited. The underlying mechanisms of the inhibition have yet to be fully elucidated. Using an Fcγ receptor–mediated NK cell activation assay, we show that ascites from ovarian cancer patients potently inhibits NK cell activation. Part of the inhibitory activity is mediated by CA125, a mucin 16 fragment shed from ovarian cancer tumors. Moreover, transcriptional analyses by RNA sequencing reveal upregulation of genes involved in multiple metabolic pathways but downregulation of genes involved in cytotoxicity and signaling pathways in NK cells purified from ovarian cancer patient ascites. Transcription of genes involved in cytotoxicity pathways are also downregulated in NK cells from healthy donors after in vitro treatment with ascites or with a CA125-enriched protein fraction. These results show that ascites and CA125 inhibit antitumor activity of NK cells at transcriptional levels by suppressing expression of genes involved in NK cell activation and cytotoxicity. Our findings shed light on the molecular mechanisms by which ascites inhibits the activity of NK cells and suggest possible approaches to reactivate NK cells for ovarian cancer immunotherapy.</jats:p> |
| first_indexed | 2024-09-23T11:38:22Z |
| format | Article |
| id | mit-1721.1/147988 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:38:22Z |
| publishDate | 2023 |
| publisher | The American Association of Immunologists |
| record_format | dspace |
| spelling | mit-1721.1/1479882023-02-10T03:31:06Z Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125 Fraser, Christopher C Jia, Bin Hu, Guangan Al Johani, Lojain Ibrahim Fritz-Klaus, Roberta Ham, James Dongjoo Fichorova, Raina N Elias, Kevin M Cramer, Daniel William Patankar, Manish S Chen, Jianzhu Massachusetts Institute of Technology. Department of Biology <jats:title>Abstract</jats:title> <jats:p>Malignant ascites is a common clinical problem in ovarian cancer. NK cells are present in the ascites, but their antitumor activity is inhibited. The underlying mechanisms of the inhibition have yet to be fully elucidated. Using an Fcγ receptor–mediated NK cell activation assay, we show that ascites from ovarian cancer patients potently inhibits NK cell activation. Part of the inhibitory activity is mediated by CA125, a mucin 16 fragment shed from ovarian cancer tumors. Moreover, transcriptional analyses by RNA sequencing reveal upregulation of genes involved in multiple metabolic pathways but downregulation of genes involved in cytotoxicity and signaling pathways in NK cells purified from ovarian cancer patient ascites. Transcription of genes involved in cytotoxicity pathways are also downregulated in NK cells from healthy donors after in vitro treatment with ascites or with a CA125-enriched protein fraction. These results show that ascites and CA125 inhibit antitumor activity of NK cells at transcriptional levels by suppressing expression of genes involved in NK cell activation and cytotoxicity. Our findings shed light on the molecular mechanisms by which ascites inhibits the activity of NK cells and suggest possible approaches to reactivate NK cells for ovarian cancer immunotherapy.</jats:p> 2023-02-09T18:02:00Z 2023-02-09T18:02:00Z 2022 2023-02-09T17:46:32Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147988 Fraser, Christopher C, Jia, Bin, Hu, Guangan, Al Johani, Lojain Ibrahim, Fritz-Klaus, Roberta et al. 2022. "Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125." Journal of immunology, 208 (9). en 10.4049/JIMMUNOL.2001095 Journal of immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf The American Association of Immunologists Prof. Chen |
| spellingShingle | Fraser, Christopher C Jia, Bin Hu, Guangan Al Johani, Lojain Ibrahim Fritz-Klaus, Roberta Ham, James Dongjoo Fichorova, Raina N Elias, Kevin M Cramer, Daniel William Patankar, Manish S Chen, Jianzhu Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125 |
| title | Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125 |
| title_full | Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125 |
| title_fullStr | Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125 |
| title_full_unstemmed | Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125 |
| title_short | Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125 |
| title_sort | ovarian cancer ascites inhibits transcriptional activation of nk cells partly through ca125 |
| url | https://hdl.handle.net/1721.1/147988 |
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