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We aimed to evaluate the PD-L1 (\n                      <jats:italic>CD274<\/jats:italic>\n                      ) expression using highly sensitive clone 73\u2009\u2212\u200910 and spatial transcriptomics (ST) analysis to elucidate the role of PD-L1 in HNSCC and thus potentially expand the pool of eligible patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Immunohistochemical staining of 73\u2009\u2212\u200910, CD3, CD4, and CD8 were performed in 94 HNSCC clinical samples along with paired adjacent squamous intraepithelial neoplasm (SIN) and normal oral mucosa (NOM) samples. The 73\u2009\u2212\u200910 positivity was evaluated using a tumor cell score\u2009\u2265\u20091%, and the results were analyzed against clinicopathological features including CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      tumor-infiltrating lymphocytes (TILs), and clinical outcomes. Furthermore, ST and PD-L1 related pathway analysis was performed in 6 paired HNSCC, SIN and NOM samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 73\u2009\u2212\u200910 detected-PD-L1 positivity was high in HNSCC (79%) compared to SIN (10%) and NOM (3%). 73\u2009\u2212\u200910\n                      <jats:sup>+<\/jats:sup>\n                      correlated with high CD4\n                      <jats:sup>+<\/jats:sup>\n                      TILs, as well as the independent prognostic factor of OS, DSS, and PFS of HNSCC (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). ST analysis revealed that the upregulated distribution of\n                      <jats:italic>CD274<\/jats:italic>\n                      correlated with 73\u2009\u2212\u200910 positivity. Pathway analysis revealed a significant upregulation of\n                      <jats:italic>CD274<\/jats:italic>\n                      and C\n                      <jats:italic>D4<\/jats:italic>\n                      in HNSCC compared to SIN and NOM, and HIF-1\u03b1 and IFN-\u03b3 as key regulators of PD-L1 expression in HNSCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Clone 73\u2009\u2212\u200910 is a relatively suitable candidate for identifying patients with PD-L1 expression eligible for ICI therapy. It demonstrates high sensitivity in detecting PD-L1 (\n                      <jats:italic>CD274<\/jats:italic>\n                      ) in HNSCC, offering immunological and prognostic insights.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12105-025-01798-8","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T09:16:05Z","timestamp":1747732565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["High-Sensitivity PD-L1 Staining Using Clone 73\u221210 Antibody and Spatial Transcriptomics for Precise Expression Analysis in Non-Tumorous, Intraepithelial Neoplasia, and Squamous Cell Carcinoma of Head and Neck"],"prefix":"10.1007","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8041-0074","authenticated-orcid":false,"given":"Yuri","family":"Noda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naho","family":"Atsumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Iwai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Tsuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"issue":"2","key":"1798_CR1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3390\/medsci11020042","volume":"11","author":"A Barsouk","year":"2023","unstructured":"Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A (2023) Epidemiology, risk factors, and prevention of head and neck squamous cell carcinoma. 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