{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:15:02Z","timestamp":1792790102566,"version":"4.5.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T00:00:00Z","timestamp":1651363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Institute of Health","award":["CA197605"],"award-info":[{"award-number":["CA197605"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30-CA14051"],"award-info":[{"award-number":["P30-CA14051"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <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 Fc\u03b3 receptor\u2013mediated 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>","DOI":"10.4049\/jimmunol.2001095","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T10:02:36Z","timestamp":1649412156000},"page":"2227-2238","source":"Crossref","is-referenced-by-count":25,"title":["Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125"],"prefix":"10.1093","volume":"208","author":[{"given":"Christopher C","family":"Fraser","sequence":"first","affiliation":[{"name":"Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology , Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3712-9225","authenticated-orcid":false,"given":"Bin","family":"Jia","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology , Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-0509","authenticated-orcid":false,"given":"Guangan","family":"Hu","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology , Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lojain Ibrahim","family":"Al Johani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin\u2013Madison , Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Fritz-Klaus","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin\u2013Madison , Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-7940","authenticated-orcid":false,"given":"James Dongjoo","family":"Ham","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology , Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raina N","family":"Fichorova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M","family":"Elias","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8024-3066","authenticated-orcid":false,"given":"Daniel William","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish S","family":"Patankar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin\u2013Madison , Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5687-6154","authenticated-orcid":false,"given":"Jianzhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology , Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,1]]},"reference":[{"key":"2025021009040797500_r1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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