{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:03:48Z","timestamp":1753891428611,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Although programmed death (PD) ligand 1 (PD-L1)\/PD-1 inhibitors show potent and durable antitumor effects in a variety of tumors, their efficacy in patients with OvCa is modest. Thus, additional immunosuppressive mechanisms beyond PD-L1\/PD-1 need to be identified.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The mRNA expression profiles of OvCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression and clinical characteristics of <jats:italic>VTCN1<\/jats:italic> (encoding B7S1) in OvCa were analyzed. The molecular interaction network, Gene Ontology (GO) analysis and Gene set enrichment analysis (GSEA) were used to functionally annotate and predict signaling pathways of <jats:italic>VTCN1<\/jats:italic> in OvCa. Moreover, 32 treatment-nai\u0308ve patients with OvCa were recruited to assess B7S1 expression. The cytotoxic immune phenotypes in distinct subgroups were analyzed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> B7S1 expression was increased in tumor sections compared with that in normal tissues from OvCa patients at both the mRNA and protein levels. <jats:italic>VTCN1<\/jats:italic> expression was significantly correlated with the mRNA expression levels of several other co-inhibitory immune checkpoints. B7S1 protein was found to be highly expressed in CD45<jats:sup>+<\/jats:sup>CD68<jats:sup>+<\/jats:sup> myeloid cells, whereas its putative receptor was expressed in CD8<jats:sup>+<\/jats:sup> tumor-infiltrating lymphocytes (TILs). Furthermore, expression of B7S1 in antigen-presenting cells (APCs) was significantly correlated with the cytolytic function of CD8<jats:sup>+<\/jats:sup> TILs. Functional annotations indicated that <jats:italic>VTCN1<\/jats:italic> was involved in regulating T cell-mediated immune responses and participated in the activation of a variety of classic signaling pathways related to the progression of human cancer.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In OvCa, B7S1 was highly expressed and may initiate dysfunction of CD8<jats:sup>+<\/jats:sup> TILs, which could be targeted for cancer immunotherapy.<\/jats:p>","DOI":"10.3389\/fmolb.2021.686803","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T10:18:07Z","timestamp":1625825887000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer"],"prefix":"10.3389","volume":"8","author":[{"given":"Dongli","family":"Cai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changgang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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