{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T07:15:08Z","timestamp":1763709308669,"version":"3.45.0"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Ovarian cancer (OvCa) is a prevalent gynecological malignancy with an increasing incidence and high mortality rate. Although the role of the herpesvirus entry mediator (HVEM), encoded by the\n                      <jats:italic>TNFRSF14<\/jats:italic>\n                      gene, is currently considered pivotal in various types of cancer, the regulation of tumor cell\u2010expressed HVEM in OvCa remains inadequately understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Specimens were used to detect HVEM expression via quantitative RT\u2010PCR and flow cytometry. The proliferation of the murine OvCa cell line ID8 was determined using the Cell Counting Kit\u20108, colony formation, and EdU staining assays. The immune constituents within the ascites fluid and spleen of tumor\u2010bearing mice were analyzed by flow cytometry. Bioinformatics analysis was performed to explore cytokines, chemokines, and signaling pathways regulated by HVEM, and differential expression levels were confirmed via quantitative RT\u2010PCR and western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Herein, we identified a significant upregulation of HVEM in OvCa tissues compared with that in benign tissues and observed dominant expression of HVEM in CD45\u207bEpCAM\u207a subsets in OvCa specimens. Tumor cell\u2010expressed HVEM was found to promote OvCa cell proliferation by partly activating spliced X\u2010box\u2010binding protein 1 (XBP1s)\u2010c\u2010Myc signaling. In mouse models, knockdown of\n                      <jats:italic>Tnfrsf14<\/jats:italic>\n                      in ID8 cells alleviated OvCa progression and specifically affected the frequency and function of T cells in the ascites fluid and spleen. In addition, tumor cell\u2010expressed HVEM altered chemokine expression (CXCL1\/9\/10\/11 and CCL2\/4\/5) and STAT signal activation (STAT5 and STAT6) in ID8 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study investigated the effects of HVEM on OvCa and validated its potential as a therapeutic marker for treating OvCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70175","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T10:25:19Z","timestamp":1742379919000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Cell\u2010Expressed Herpesvirus Entry Mediator Regulates Proliferation and Adaptive Immunity in Ovarian Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4291-1115","authenticated-orcid":false,"given":"Yun","family":"Lu","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine Tongji University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2573-6079","authenticated-orcid":false,"given":"Yijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine Tongji University Shanghai 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