{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:51:30Z","timestamp":1793055090183,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp;amp; Neck"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Olfactory neuroblastoma (ONB) is a rare sinonasal malignancy with limited therapeutic options in the recurrent\/metastatic setting; little is known regarding its responsiveness to immunotherapy. Inhibition of enhancer of zeste homolog 2 (EZH2) has been shown to improve T\u2010cell\u2010mediated killing and susceptibility to immune checkpoint inhibitors in a variety of cancers. We aimed to evaluate the expression and activity of EZH2 in ONB and its association with immune characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We studied a cohort of 36 ONB real\u2010world patient samples that underwent molecular profiling at a centralized lab (Caris Life Science). To infer EZH2 methyltransferase activity, we adopted an EZH2 gene repression signature (ERS) score: ONB samples were stratified into ERS\u2010low and ERS\u2010high subgroups, corresponding to high and low inferred EZH2 methyltransferase activity, respectively. Transcriptomic data were utilized to calculate the T\u2010cell\u2010inflamed (TCI) score and mitogen\u2010activated protein kinase (MAPK) pathway activation score (MPAS). Tumor immune microenvironment composition was inferred from tumor\u2010derived bulk RNA sequencing data. We analyzed immunologic differences between ERS\u2010low and ERS\u2010high ONB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In ERS\u2010high ONB, we observed a higher expression of immune\u2010related genes, a higher proportion of TCI tumors, and an enrichment in inflammatory pathways. ERS\u2010high ONB also displayed increased macrophages, and to a lesser extent, B cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration in the tumor microenvironment. Also, ERS\u2010high was associated with increased MPAS, potentially identifying ONB with increased susceptibility to MAPK inhibitors. These data were confirmed in an independent validation cohort using a publicly available dataset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, our data suggest that low EZH2 activity is associated with a more immunogenic microenvironment, paving the way for potential combinations of EZH2 inhibitors with checkpoint blockade in ONB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70076","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:25:08Z","timestamp":1762943108000},"page":"932-940","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genomic and Immune Correlates of\n                    <scp>EZH2<\/scp>\n                    Expression and Activity in Olfactory Neuroblastoma"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-9555","authenticated-orcid":false,"given":"Elisabetta","family":"Xue","sequence":"first","affiliation":[{"name":"Center for Immuno\u2010Oncology CCR, NCI, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolulope","family":"Adeyelu","sequence":"additional","affiliation":[{"name":"CARIS Life Sciences  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris","family":"Krause","sequence":"additional","affiliation":[{"name":"CARIS Life Sciences  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Elliott","sequence":"additional","affiliation":[{"name":"CARIS Life Sciences  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranee","family":"Mehra","sequence":"additional","affiliation":[{"name":"University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heloisa","family":"Soares","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Lou","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Vanderwalde","sequence":"additional","affiliation":[{"name":"CARIS Life Sciences  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Spetzler","sequence":"additional","affiliation":[{"name":"CARIS Life Sciences  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"Bracken\u2010Clarke","sequence":"additional","affiliation":[{"name":"Center for Immuno\u2010Oncology CCR, NCI, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Nyall R.","family":"London","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Sinonasal and Skull Base Tumor Section, Surgical Oncology Program, CCR, NCI, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Gulley","sequence":"additional","affiliation":[{"name":"Center for Immuno\u2010Oncology CCR, NCI, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalampos S.","family":"Floudas","sequence":"additional","affiliation":[{"name":"Center for 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