{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:41:31Z","timestamp":1780926091512,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1011647"],"award-info":[{"award-number":["2020R1C1C1011647"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2023R1A2C1003096"],"award-info":[{"award-number":["2023R1A2C1003096"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2023R1A2C3002835"],"award-info":[{"award-number":["2023R1A2C3002835"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>\n                    Immune checkpoint blockers (ICBs) targeting programmed cell death protein 1 (PD\u20101) have been proven to be an effective first\u2010line therapy against programmed cell death 1 ligand 1 (\n                    <jats:italic>PD\u2010L1<\/jats:italic>\n                    ; also known as CD274 molecule)\u2010expressing head and neck squamous cell carcinoma (HNSCC) in recent KEYNOTE\u2010048 trial. However, associated changes in the tumor microenvironment (TME) and underlying mechanisms remain elusive. Oral tumors in C57\/BL6 mice were induced by administering 7,12\u2010dimethylbenzanthracene into the buccal mucosa. Single\u2010cell suspension was isolated from tumor tissue; proliferating cells were injected subcutaneously into the left flank of mice to establish Ajou oral cancer (AOC) cell lines. Subsequently, a syngeneic\n                    <jats:italic>PD\u2010L1<\/jats:italic>\n                    \u2010expressing HNSCC model was developed by injecting AOC cells into the buccal or tongue area. The model recapitulated human HNSCC molecular features and showed reliable\n                    <jats:italic>in vivo<\/jats:italic>\n                    tumorigenicity with significant\n                    <jats:italic>PD\u2010L1<\/jats:italic>\n                    expression. ICB monotherapy induced global changes in the TME, including vascular normalization. Furthermore, the antitumor effect of ICB monotherapy was superior to those of other therapeutic agents, including cisplatin and inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2). The ICB\u2010induced antitumorigenicity and TME normalization were alleviated by blocking the type I interferon pathway. In summary, ICB monotherapy is sufficient to induce TME normalization in the syngeneic model; the type I interferon pathway is indispensable in realizing the effects of ICBs. Furthermore, these results explain the underlying mechanism of the efficacy of ICB monotherapy against\n                    <jats:italic>PD\u2010L1<\/jats:italic>\n                    \u2010expressing HNSCC in the KEYNOTE\u2010048 trial.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13633","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T03:55:02Z","timestamp":1710993302000},"page":"1923-1939","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Immune checkpoint inhibitor monotherapy is sufficient to promote microenvironmental normalization via the type I\u00a0interferon pathway in\n                    <i>PD\u2010L1<\/i>\n                    \u2010expressing head and neck cancer"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-4896","authenticated-orcid":false,"given":"Jeon Yeob","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Ajou University School of Medicine  Suwon Korea"},{"name":"Department of Biomedical Sciences Ajou University Graduate School of Medicine  Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0896-2883","authenticated-orcid":false,"given":"Bok\u2010Soon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ajou University School of Medicine  Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ajou University School of Medicine  Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chorong","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ajou University School of Medicine  Suwon 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