{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:07:05Z","timestamp":1772118425007,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"publisher","award":["693786"],"award-info":[{"award-number":["693786"]}],"id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Head and neck squamous cell carcinoma (HNSCC) is linked to human papillomavirus (HPV) infection. HPV\u2010positive and HPV\u2010negative HNSCC exhibit distinct molecular and clinical characteristics. Although checkpoint inhibitors have shown efficiency in recurrent\/metastatic HNSCC, response variability persists regardless of HPV status. This study aimed to explore the CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell landscape in HPV\u2010negative HNSCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed simultaneous single\u2010cell RNA and TCR sequencing of CD8\n                      <jats:sup>+<\/jats:sup>\n                      tumor\u2010infiltrating lymphocytes (TILs) from treatment\u2010na\u00efve HPV\u2010negative HNSCC patients. Additionally, cells were stimulated ex vivo, which allowed for the tracking of clonal transcriptomic responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis identified a subset of CD8\n                      <jats:sup>+<\/jats:sup>\n                      TILs highly enriched for interferon\u2010stimulated genes (ISG). TCR analysis revealed ISG cells are clonally related to a population of granzyme K (GZMK)\u2010expressing cells. However, unlike GZMK cells, which exhibited rapid effector\u2010like phenotypes following stimulation, ISG cells were transcriptionally inert. Additionally, ISG cells showed specific enrichment within tumor and were found across multiple tumor entities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      ISG\u2010enriched CD8\n                      <jats:sup>+<\/jats:sup>\n                      TILs are a consistent feature of various tumor entities. These cells are poorly understood but possess characteristics that may impact antitumor immunity. Understanding the unique properties and functionality of ISG cells could offer innovative treatment approaches to improve patient outcomes in HPV\u2010negative HNSCC and other cancer types.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/eji.202451371","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T03:10:57Z","timestamp":1731381057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type I Interferon Drives a Cellular State Inert to TCR\u2010Stimulation and Could Impede Effective T\u2010Cell Differentiation in Cancer"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0683-1369","authenticated-orcid":false,"given":"Dillon","family":"Corvino","sequence":"first","affiliation":[{"name":"Tumor\u2010Immunobiology Institute for Experimental Oncology University Hospital Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Batstone","sequence":"additional","affiliation":[{"name":"Royal Brisbane and Women's Hospital  Brisbane Queensland Australia"},{"name":"Faculty of Medicine University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett G. 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