{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:44:36Z","timestamp":1792104276412,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Predictive biomarkers for response to PD\u20101 blockade in recurrent or metastatic HNSCC remain limited. We investigated whether coordinated expression of multiple inhibitory immune checkpoints defines a clinically relevant biomarker phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical and immunohistochemical data from 78 patients with recurrent or metastatic HNSCC treated with nivolumab or pembrolizumab were retrospectively analyzed. Expression of PD\u2010L1, LAG\u20103, TIM\u20103, and IDO1 on tumor\u2010infiltrating immune cells was assessed. A composite immune checkpoint phenotype was defined by concurrent immune\u2010cell expression of these markers. Associations with treatment response and survival were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The composite immune checkpoint phenotype was observed in 10.1% of tumors and was strongly associated with objective response (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), disease control (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), and improved overall, disease\u2010specific, and progression\u2010free survival (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.030). In multivariable analysis, this phenotype independently predicted overall (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031) and disease\u2010specific survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Coordinated expression of multiple inhibitory immune checkpoints identifies an inflamed tumor microenvironment associated with improved outcomes following PD\u20101 blockade in HNSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70313","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T01:56:01Z","timestamp":1778464561000},"page":"2871-2882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comprehensive Immune Checkpoint Phenotype Predicts Response and Survival to\n                    <scp>PD<\/scp>\n                    \u20101 Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6822-3089","authenticated-orcid":false,"given":"Mathias","family":"Fiedler","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"},{"name":"Department of Oral and Maxillofacial Surgery Center for Medical Biotechnology, University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Baumann","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"},{"name":"Institute of Pathology, University of Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Eichberger","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"},{"name":"Department of Oral and Maxillofacial Surgery Center for Medical Biotechnology, University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Gottsauner","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes G.","family":"Schuderer","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"},{"name":"Department of Oral and Maxillofacial Surgery Center for Medical Biotechnology, University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes K.","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"},{"name":"Department of Oral and Maxillofacial Surgery Center for Medical Biotechnology, University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Poeck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III Hematology &amp; Internal Oncology, University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Grube","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III Hematology &amp; Internal Oncology, University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gerken","sequence":"additional","affiliation":[{"name":"Center of Tumor Registry, University of Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten E.","family":"Reichert","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-5351","authenticated-orcid":false,"given":"Tobias","family":"Ettl","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery University Hospital Regensburg  Regensburg Germany"},{"name":"Department of Oral and Maxillofacial Surgery Center for Medical Biotechnology, University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00224-3"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2018.03.006"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01550-6"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-025-01020-6"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1715715"},{"key":"e_1_2_12_7_1","first-page":"1","article-title":"Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges","volume":"42","author":"Wise\u2010Draper T. 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