{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:37:10Z","timestamp":1761863830839,"version":"3.37.3"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute of National Institute of Health","doi-asserted-by":"publisher","award":["R01 HL089405","R01 HL115265"],"award-info":[{"award-number":["R01 HL089405","R01 HL115265"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,21]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Ovarian cancers are known to evade immunosurveillance and to orchestrate a suppressive immune microenvironment. Here we examine the role of human epididymis protein 4 (HE4), an ovarian cancer biomarker, in immune evasion. Through modified subtractive hybridization analyses we have characterized the gene targets of HE4 in human peripheral blood mononuclear cells (PBMCs), and established a preliminary mechanism for HE4-mediated immune failure in ovarian tumours. Upon exposure of purified PMBCs to HE4, osteopontin (OPN) and dual-specificity phosphatase 6 (DUSP6) emerged as the most suppressed and up-regulated genes, respectively. SKOV3 and OVCAR8, human ovarian carcinoma cell lines, exhibited enhanced proliferation in conditioned media from HE4-exposed PBMCs, an effect that was attenuated by the addition of recombinant OPN or OPN-inducible cytokines [interleukin (IL)-12 and interferon (IFN)-\u0194]. Additionally, upon co-culture with PBMCs, HE4-silenced SKOV3 cells were found to be more susceptible to cytotoxic cell death. The relationship between HE4 and OPN was reinforced further through the analysis of serous ovarian cancer patient samples. In these biopsy specimens, the number of OPN+ T cells correlated positively with progression free survival (PFS) and inversely with serum HE4 level. Taken together, these findings show that HE4 enhances ovarian cancer tumorigenesis by compromising OPN-mediated T cell activation.<\/jats:p>","DOI":"10.1111\/cei.13153","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T09:19:57Z","timestamp":1525943997000},"page":"327-340","source":"Crossref","is-referenced-by-count":11,"title":["HE4 suppresses the expression of osteopontin in mononuclear cells and compromises their cytotoxicity against ovarian cancer cells"],"prefix":"10.1093","volume":"193","author":[{"given":"N E","family":"James","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA"},{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Cantillo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M T","family":"Oliver","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R B","family":"Rowswell-Turner","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Rhode Island, Kingston, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J R","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K-K","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Rhode Island, Kingston, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"C O","family":"Chichester","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P A","family":"DiSilvestro","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R G","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Rhode Island, Kingston, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R K","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA"},{"name":"Department of Pharmacy, University of Rhode Island, Kingston, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T C","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Surgery, Roger Williams Medical Center, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"2021120808394799900_cei13153-bib-0001","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1095\/biolreprod45.2.350","article-title":"A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors","volume":"45","author":"Kirchhoff","year":"1991","journal-title":"Biol Reprod"},{"key":"2021120808394799900_cei13153-bib-0002","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S1093-3263(99)00023-6","article-title":"The whey acidic protein family: a new signature motif and three-dimensional structure by comparative modeling","volume":"17","author":"Ranganathan","year":"1999","journal-title":"J Mol Graph 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