{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:40:58Z","timestamp":1769514058993,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":27,"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":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>E2F transcription factors are well\u2010recognized oncogenic molecules, and their correlation with immune cell infiltration has recently been reported. This work studies the impacts and mechanism of E2F transcription factor 3 (E2F3) in the growth and tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Aberrantly expressed transcription factors in NPC were screened by abundant bioinformatics analyses. Gene expression in NPC cells was analyzed by reverse\u00a0transcription\u2010quantitative polymerase chain reaction and\u00a0Western blot analyses. Malignant behaviors of NPC cells were analyzed by cell counting kit\u20108, 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine labeling, Transwell assays, and xenograft tumor models. TPA\u2010induced THP\u20101 cells (macrophages) were cultured in the conditioned medium of NPC cells to mimic tumor\u2010associated macrophages (TAMs) in vivo, and these TAMs were cocultured with CD8<jats:sup>+<\/jats:sup> T cells. Regulation of E2F3 on protein regulator of cytokinesis 1 (PRC1) and baculoviral IAP repeat containing 5 (BIRC5) was validated by chromatin immunoprecipitation and luciferase reporter assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>E2F3 was highly expressed in NPC cells, and its knockdown suppressed malignant behavior and tumorigenic ability of the cells. The E2F3 knockdown condition downregulated M2 cytokines CD163 and interleukin\u201010 in TAMs, which further enhanced proliferation and activation of the cocultured CD8<jats:sup>+<\/jats:sup> T cells. E2F3 promoted transcription of PRC1 and BRIC5. Furthermore,\u00a0PRC1 or BRIC5 upregulation in NPC cells restored the malignant properties of NPC cells, reprogrammed the TAMs to M2 phenotype, and suppressed the CD8<jats:sup>+<\/jats:sup> T cell proliferation and activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This work suggests that E2F3 renders an immunosuppressive TME in NPC by activating PRC1 and BIRC5. Suppression of any member involved might favor tumor elimination.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.987","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T11:57:23Z","timestamp":1693223843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["E2F3 renders an immunosuppressive tumor microenvironment in nasopharyngeal carcinoma: Involvements of the transcription activation of PRC1 and BIRC5"],"prefix":"10.1002","volume":"11","author":[{"given":"Qiang","family":"Wang","sequence":"first","affiliation":[{"name":"Otolaryngology &amp; Head and Neck Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital Hangzhou Medical College Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Yu","sequence":"additional","affiliation":[{"name":"Otolaryngology &amp; Head and Neck Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital Hangzhou Medical College Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-3577","authenticated-orcid":false,"given":"Yueyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Otolaryngology &amp; Head and Neck Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital Hangzhou Medical College Hangzhou Zhejiang 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